tetrahydrouridine profile

Tetrahydrouridine: An inhibitor of nucleotide metabolism. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	13391465
SCHEMBL ID	171865
MeSH ID	M0021239

ID Source

PubMed CID

13391465

SCHEMBL ID

171865

MeSH ID

M0021239

Synonym
tetrahydrouridine
SCHEMBL171865

Synonym

tetrahydrouridine

SCHEMBL171865

Excerpt	Reference	Relevance
" It was observed that 5-Med-Cyd exerts its effects via deamination to thymidine, which is particularly toxic to human promyelocytic (HL-60) and T-cell (JM) leukemia cell lines in vitro."	( Reversal of deamination-related cytotoxicity of 5-methyl-2'-deoxycytidine by tetrahydrouridine in human leukemia cells. Jekunen, A; Vilpo, JA, 1984)	0.27

Excerpt

Reference

Relevance

" It was observed that 5-Med-Cyd exerts its effects via deamination to thymidine, which is particularly toxic to human promyelocytic (HL-60) and T-cell (JM) leukemia cell lines in vitro."

( Reversal of deamination-related cytotoxicity of 5-methyl-2'-deoxycytidine by tetrahydrouridine in human leukemia cells.
Jekunen, A; Vilpo, JA, 1984)

0.27

Excerpt	Reference	Relevance
" This paper describes our preclinical studies to determine the pharmacokinetic properties of CDC and the disposition of the drug, both alone and in the presence of the metabolic modulator tetrahydrouridine (THU), a cytidine deaminase inhibitor."	( Analytical and pharmacokinetic studies with 5-chloro-2'-deoxycytidine. Bigelow, JC; Hale, JT; Mathews, LA; McCormack, JJ, 2002)	0.31
" Plasma pharmacokinetic parameters were calculated compartmentally and non-compartmentally."	( Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice. Beumer, JH; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Florian, JA; Joseph, E; Kay, B; Parise, RA; Parker, RS, 2008)	0.35
" Plasma and urine pharmacokinetic parameters were calculated non-compartmentally and compartmentally."	( Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice. Ames, MM; Bai, L; Beumer, JH; Clausen, DM; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Gilbert, JA; Hershberger, PA; Holleran, JL; Parise, RA; Yellow-Duke, AE, 2011)	0.37
" Pharmacokinetic evaluation was carried out in cynomolgus monkeys in support of an ongoing phase I study of the PO combination of FdCyd and the CD inhibitor tetrahydrouridine (THU; NSC112907)."	( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)	0.42
" A pilot pharmacokinetic study was performed in humans to assess FdCyd bioavailability."	( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)	0.42
" FdCyd half-life ranged between 22 and 56 min, and clearance was approximately 15 mL/min/kg."	( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)	0.42

Excerpt

Reference

Relevance

" This paper describes our preclinical studies to determine the pharmacokinetic properties of CDC and the disposition of the drug, both alone and in the presence of the metabolic modulator tetrahydrouridine (THU), a cytidine deaminase inhibitor."

( Analytical and pharmacokinetic studies with 5-chloro-2'-deoxycytidine.
Bigelow, JC; Hale, JT; Mathews, LA; McCormack, JJ, 2002)

0.31

" Plasma pharmacokinetic parameters were calculated compartmentally and non-compartmentally."

( Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice.
Beumer, JH; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Florian, JA; Joseph, E; Kay, B; Parise, RA; Parker, RS, 2008)

0.35

" Plasma and urine pharmacokinetic parameters were calculated non-compartmentally and compartmentally."

( Plasma pharmacokinetics and oral bioavailability of the 3,4,5,6-tetrahydrouridine (THU) prodrug, triacetyl-THU (taTHU), in mice.
Ames, MM; Bai, L; Beumer, JH; Clausen, DM; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Gilbert, JA; Hershberger, PA; Holleran, JL; Parise, RA; Yellow-Duke, AE, 2011)

0.37

" Pharmacokinetic evaluation was carried out in cynomolgus monkeys in support of an ongoing phase I study of the PO combination of FdCyd and the CD inhibitor tetrahydrouridine (THU; NSC112907)."

( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans.
Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)

0.42

" A pilot pharmacokinetic study was performed in humans to assess FdCyd bioavailability."

0.42

" FdCyd half-life ranged between 22 and 56 min, and clearance was approximately 15 mL/min/kg."

0.42

Excerpt	Reference	Relevance
"The antiviral activity and cytotoxicity of (E)-5-(2-bromovinyl)-2'-deoxycytidine (BrVdCyd) against herpes simplex virus type 1 (HSV-1), singly and in combination with deaminase inhibitors was determined using rabbit kidney (RK-13), HEP-2, BHK-21 and VERO cells."	( Antiherpes virus activity and effect on deoxyribonucleoside triphosphate pools of (E)-5-(2-bromovinyl)-2'-deoxycytidine in combination with deaminase inhibitors. Aduma, PJ; De Clercq, E; Gupta, SV, 1990)	0.28
"Decitabine (5-aza-2'-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia."	( Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Chan, K; Covey, JM; Engelke, K; Ling, Y; Saunthararajah, Y; Sharpnack, D; Terse, P, )	0.13

Excerpt

Reference

Relevance

"The antiviral activity and cytotoxicity of (E)-5-(2-bromovinyl)-2'-deoxycytidine (BrVdCyd) against herpes simplex virus type 1 (HSV-1), singly and in combination with deaminase inhibitors was determined using rabbit kidney (RK-13), HEP-2, BHK-21 and VERO cells."

( Antiherpes virus activity and effect on deoxyribonucleoside triphosphate pools of (E)-5-(2-bromovinyl)-2'-deoxycytidine in combination with deaminase inhibitors.
Aduma, PJ; De Clercq, E; Gupta, SV, 1990)

0.28

"Decitabine (5-aza-2'-deoxycytidine; DAC) in combination with tetrahydrouridine (THU) is a potential oral therapy for sickle cell disease and β-thalassemia."

( Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice.
Chan, K; Covey, JM; Engelke, K; Ling, Y; Saunthararajah, Y; Sharpnack, D; Terse, P, )

0.13

Excerpt	Reference	Relevance
"Rectal bioavailability of Ara-C (serum AUC 4 h: 65 micrograms h-1 ml-1) administered in a suppository formulation containing tetrahydrouridine (a deamination inhibitor) and sodium salicylate (an adjuvant) to dogs was better than that from a suppository formulation without tetrahydrouridine (serum AUC 4 h: 18 micrograms h-1 ml-1)."	( Enhanced serum concentrations of Ara-C using suppositories containing tetrahydrouridine as a deamination inhibitor of Ara-C. Engle, KK; Higuchi, T; Liversidge, GG; Nishihata, T, 1986)	0.27
" Therefore, we characterized the THU pharmacokinetics and bioavailability in mice."	( Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice. Beumer, JH; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Florian, JA; Joseph, E; Kay, B; Parise, RA; Parker, RS, 2008)	0.35
" and orally substantially increased oral bioavailability of dFdC."	( Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine. Beumer, JH; Covey, JM; Egorin, MJ; Eiseman, JL; Joseph, E; Parise, RA, 2008)	0.35
" Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC."	( Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice. Chan, K; Covey, JM; Engelke, K; Ling, Y; Saunthararajah, Y; Sharpnack, D; Terse, P, )	0.13
" FdCyd PO bioavailability after THU ranged between 9 and 25 % and increased with increasing THU dose."	( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)	0.42
"Tetrahydrouridine and decitabine were rapidly absorbed into the systemic circulation after a single combination oral dose, with relative bioavailability of decitabine ≥74% in fasted males compared with separate oral administration of THU followed by decitabine 1 h later."	( Pharmacokinetics and pharmacodynamics of an oral formulation of decitabine and tetrahydrouridine. Clausen, WHO; Friedrich, U; Jacobberger, JW; Lau, H; Saunthararajah, Y; Woost, PG, 2023)	0.91

Excerpt

Reference

Relevance

"Rectal bioavailability of Ara-C (serum AUC 4 h: 65 micrograms h-1 ml-1) administered in a suppository formulation containing tetrahydrouridine (a deamination inhibitor) and sodium salicylate (an adjuvant) to dogs was better than that from a suppository formulation without tetrahydrouridine (serum AUC 4 h: 18 micrograms h-1 ml-1)."

( Enhanced serum concentrations of Ara-C using suppositories containing tetrahydrouridine as a deamination inhibitor of Ara-C.
Engle, KK; Higuchi, T; Liversidge, GG; Nishihata, T, 1986)

0.27

" Therefore, we characterized the THU pharmacokinetics and bioavailability in mice."

0.35

" and orally substantially increased oral bioavailability of dFdC."

( Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine.
Beumer, JH; Covey, JM; Egorin, MJ; Eiseman, JL; Joseph, E; Parise, RA, 2008)

0.35

" Tetrahydrouridine, a competitive inhibitor of cytidine deaminase, was used in the combination to improve oral bioavailability of DAC."

( Subchronic oral toxicity study of decitabine in combination with tetrahydrouridine in CD-1 mice.
Chan, K; Covey, JM; Engelke, K; Ling, Y; Saunthararajah, Y; Sharpnack, D; Terse, P, )

0.13

" FdCyd PO bioavailability after THU ranged between 9 and 25 % and increased with increasing THU dose."

0.42

"Tetrahydrouridine and decitabine were rapidly absorbed into the systemic circulation after a single combination oral dose, with relative bioavailability of decitabine ≥74% in fasted males compared with separate oral administration of THU followed by decitabine 1 h later."

( Pharmacokinetics and pharmacodynamics of an oral formulation of decitabine and tetrahydrouridine.
Clausen, WHO; Friedrich, U; Jacobberger, JW; Lau, H; Saunthararajah, Y; Woost, PG, 2023)

0.91

Excerpt	Relevance	Reference
" We describe here the evaluation of 2',3'-dideoxycytidine (ddC) against FeLV-FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants."	( Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy. Hill, DL; Hoover, EA; Mullins, JI; Perigo, NA; Quackenbush, SL; Strobel, JD; Zeidner, NS, 1989)	0.28
" In tumor tissue, optimal doses of FUra or FdUrd resulted in lower (a) FdUMP levels (5- to 2-fold), (b) RNA-level antimetabolites (6- to 3-fold), and (c) DNA-level antimetabolites (10- to 4-fold) compared to an optimal dosage of FdCyd plus H4Urd."	( Tumor-selective metabolism of 5-fluoro-2'-deoxycytidine coadministered with tetrahydrouridine compared to 5-fluorouracil in mice bearing Lewis lung carcinoma. Boothman, DA; Briggle, TV; Greer, S, 1987)	0.27
" Mice were dosed with THU iv (100 mg/kg) or po (30, 100, or 300 mg/kg)."	( Plasma pharmacokinetics and oral bioavailability of 3,4,5,6-tetrahydrouridine, a cytidine deaminase inhibitor, in mice. Beumer, JH; Covey, JM; D'Argenio, DZ; Egorin, MJ; Eiseman, JL; Florian, JA; Joseph, E; Kay, B; Parise, RA; Parker, RS, 2008)	0.35
" We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC."	( Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine. Beumer, JH; Covey, JM; Egorin, MJ; Eiseman, JL; Joseph, E; Parise, RA, 2008)	0.35
"Coadministration of THU enables oral dosing of dFdC and warrants clinical testing."	( Modulation of gemcitabine (2',2'-difluoro-2'-deoxycytidine) pharmacokinetics, metabolism, and bioavailability in mice by 3,4,5,6-tetrahydrouridine. Beumer, JH; Covey, JM; Egorin, MJ; Eiseman, JL; Joseph, E; Parise, RA, 2008)	0.35
" Such variability, which may lead to treatment failure or toxicity, could need drug concentration measurement to individualize dosing regimen."	( An APCI LC-MS/MS method for routine determination of capecitabine and its metabolites in human plasma. Bérard, M; Demarchi, M; Kantelip, JP; Montange, D; Muret, P; Piédoux, S; Royer, B, 2010)	0.36
"Animals were dosed intravenously (IV) or per os (PO)."	( Oral and intravenous pharmacokinetics of 5-fluoro-2'-deoxycytidine and THU in cynomolgus monkeys and humans. Beumer, JH; Covey, JM; Davis, M; Doroshow, JH; Eiseman, JL; Holleran, JL; Johnson, WD; Kummar, S; McCormick, DL; Newman, EM, 2015)	0.42

Excerpt

Relevance

Reference

" We describe here the evaluation of 2',3'-dideoxycytidine (ddC) against FeLV-FAIDS infection - both in vitro in cell culture assay systems and in vivo in cats administered ddC either via intravenous bolus dosage or via controlled release subcutaneous implants."

( Feline leukemia virus-induced immunodeficiency syndrome in cats as a model for evaluation of antiretroviral therapy.
Hill, DL; Hoover, EA; Mullins, JI; Perigo, NA; Quackenbush, SL; Strobel, JD; Zeidner, NS, 1989)

0.28

" In tumor tissue, optimal doses of FUra or FdUrd resulted in lower (a) FdUMP levels (5- to 2-fold), (b) RNA-level antimetabolites (6- to 3-fold), and (c) DNA-level antimetabolites (10- to 4-fold) compared to an optimal dosage of FdCyd plus H4Urd."

( Tumor-selective metabolism of 5-fluoro-2'-deoxycytidine coadministered with tetrahydrouridine compared to 5-fluorouracil in mice bearing Lewis lung carcinoma.
Boothman, DA; Briggle, TV; Greer, S, 1987)

0.27

" Mice were dosed with THU iv (100 mg/kg) or po (30, 100, or 300 mg/kg)."

0.35

" We investigated the ability of THU to decrease elimination and first-pass effect by CD, thereby enabling oral dosing of dFdC."

0.35

"Coadministration of THU enables oral dosing of dFdC and warrants clinical testing."

0.35

" Such variability, which may lead to treatment failure or toxicity, could need drug concentration measurement to individualize dosing regimen."

( An APCI LC-MS/MS method for routine determination of capecitabine and its metabolites in human plasma.
Bérard, M; Demarchi, M; Kantelip, JP; Montange, D; Muret, P; Piédoux, S; Royer, B, 2010)

0.36

"Animals were dosed intravenously (IV) or per os (PO)."

0.42

Research

Studies (116)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	61 (52.59)	18.7374
1990's	17 (14.66)	18.2507
2000's	13 (11.21)	29.6817
2010's	17 (14.66)	24.3611
2020's	8 (6.90)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe

Studies, This Drug (%)

All Drugs %

pre-1990

61 (52.59)

18.7374

1990's

17 (14.66)

18.2507

2000's

13 (11.21)

29.6817

2010's

17 (14.66)

24.3611

2020's

8 (6.90)

2.80

[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	9 (7.38%)	5.53%
Reviews	3 (2.46%)	6.00%
Case Studies	3 (2.46%)	4.05%
Observational	0 (0.00%)	0.25%
Other	107 (87.70%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type

This drug (%)

All Drugs (%)

Trials

9 (7.38%)

5.53%

Reviews

3 (2.46%)

6.00%

Case Studies

3 (2.46%)

4.05%

Observational

0 (0.00%)

0.25%

Other

107 (87.70%)

84.16%

[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (17)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Phase I Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) in Myeloid Leukemia and MDS [NCT01041443]	Phase 1	25 participants (Actual)	Interventional	2009-12-31	Completed
An Open-Label, Randomized, Four-Period, Three-Block, Pharmacokinetic Study of Three Formulations of Decitabine/Tetrahydrouridine (THU) Combination Modified Release Capsules in Healthy Adults Under Fasting and Fed Conditions [NCT04086238]	Phase 1	46 participants (Actual)	Interventional	2019-10-08	Completed
Phase I Evaluation of Adjuvant Oral Decitabine and Tetrahydrouridine With or Without Celecoxib in Patients Undergoing Pulmonary Metastasectomy [NCT02839694]	Phase 1	0 participants (Actual)	Interventional	2016-07-07	Withdrawn
An Open Label, Randomized, Single Dose, Two Way Crossover, Bioavailability Study of a Combination Formulation of Decitabine/Tetrahydrouridine (2.5 mg/100 mg) Modified Release Capsules in Healthy, Fasting, Male Adults [NCT05816356]	Phase 1	10 participants (Anticipated)	Interventional	2023-03-24	Recruiting
Phase I/II Evaluation of Oral Decitabine/Tetrahydrouridine as Epigenetic Priming for Pembrolizumab Immune Checkpoint Blockade in Inoperable Locally Advanced or Metastatic Non-Small Cell Lung Cancers, Esophageal Carcinomas, or Pleural Mesotheliomas [NCT03233724]	Phase 1/Phase 2	9 participants (Actual)	Interventional	2018-04-11	Terminated(stopped due to Study terminated due to drug supply issues.)
p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Advanced Pancreatic Cancer That Has Progressed Through One or More Lines of Therapy [NCT02847000]	Early Phase 1	13 participants (Actual)	Interventional	2016-12-20	Completed
A Multi-Histology Phase II Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) [NCT00978250]	Phase 2	95 participants (Actual)	Interventional	2009-08-20	Completed
p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies [NCT02846935]	Early Phase 1	7 participants (Actual)	Interventional	2017-04-25	Completed
A Multicentre Trial Evaluating the Efficacy and Safety of Oral Decitabine Tetrahydrouridine (NDec) in Patients With Sickle Cell Disease [NCT05405114]	Phase 2	84 participants (Anticipated)	Interventional	2022-07-07	Recruiting
Phase II Evaluation of Nivolumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Decitabine/Tetrahydrouridine as Second Line Therapy for Non-small Cell Lung Cancer [NCT02664181]	Phase 2	13 participants (Actual)	Interventional	2017-06-06	Active, not recruiting
Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With External Brain Radiation for Metastatic Carcinoma to the Brain [NCT00521183]	Phase 1	2 participants (Actual)	Interventional	2007-06-30	Completed
Translational Phase I Trial of Escalating Doses of 5-Chloro-2'-Deoxycytidine (CldC) With a Fixed Dose of Tetrahydrouridine Combined With a Fixed Dose of Cisplatin Concomitant With Definitive Radiation in Patients With Advanced Squamous Cell Carcinoma of t [NCT00077051]	Phase 1	1 participants (Actual)	Interventional	2004-04-30	Completed
Phase 0 Trial of [F-18]-5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine [NCT01479348]	Early Phase 1	5 participants (Actual)	Interventional	2011-11-01	Terminated(stopped due to Slow, insufficient accrual.)
Phase 1 Study of Oral Decitabine and Tetrahydrouridine (THU) in Patients With High Risk Sickle Cell Disease [NCT01685515]	Phase 1	25 participants (Actual)	Interventional	2012-08-31	Completed
An Open-Label, Randomized, Single-Dose, Four-Way Crossover, Bioavailability Study of Three Formulations of Decitabine/Tetrahydrouridine (THU) Combination Modified Release Capsules (5 mg/250 mg) in Healthy and Fasting Adults [NCT03828084]	Phase 1	16 participants (Actual)	Interventional	2019-04-03	Completed
Phase I Trial of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine [NCT00359606]	Phase 1	58 participants (Actual)	Interventional	1999-04-30	Completed
Proof-of-concept Study of Nicotinamide and Oral Tetrahydrouridine (THU) and Decitabine to Treat High Risk Sickle Cell Disease [NCT04055818]	Phase 1	20 participants (Anticipated)	Interventional	2020-01-24	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00978250 (3) [back to overview]	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).
NCT00978250 (3) [back to overview]	Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)
NCT00978250 (3) [back to overview]	Progression-free Survival (PFS)
NCT01479348 (4) [back to overview]	Number of Participants With Serious and Non-Serious Adverse Events
NCT01479348 (4) [back to overview]	Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
NCT01479348 (4) [back to overview]	Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans
NCT01479348 (4) [back to overview]	Tumor to Background Ratios (TBRs) of Target Lesions at 4 Time Points After Injection
NCT02664181 (2) [back to overview]	Overall Survival
NCT02664181 (2) [back to overview]	Time-to-Progression
NCT03233724 (5) [back to overview]	Maximum Tolerated Dose (MTD) of Decitabine
NCT03233724 (5) [back to overview]	Maximum Tolerated Dose (MTD) of Tetrahydrouridine
NCT03233724 (5) [back to overview]	Number of Participants With a Dose Limiting Hematologic Toxicity (DLT)
NCT03233724 (5) [back to overview]	Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
NCT03233724 (5) [back to overview]	Overall Response Rate

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT00978250)
Timeframe: Date treatment consent signed to date off study, approximately 109 months and 16 days.

Intervention	Participants (Count of Participants)
5-Fluro-2'-Deoxycytidine (FdCyd) + Tetrahydrouridine (THU)	91

[back to top]

Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)

Response was measured using the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of the LD. (NCT00978250)
Timeframe: until subject progressed or went off study for other reasons (up to approximately 1 year)

Intervention	percentage of participants (Number)
Non-Small Cell Cancer Stratum	0.0
Breast Cancer Stratum	6.9
Bladder Cancer Stratum	5.6
Head and Neck Cancer Stratum	0.0

[back to top]

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new lesions. (NCT00978250)
Timeframe: until subject progressed or went off study for other reasons (up to approximately 1 year)

Intervention	months (Median)
Non-Small Cell Cancer Stratum	2.3
Breast Cancer Stratum	3.7
Bladder Cancer Stratum	3.6
Heand and Neck Cancer Stratum	1.7

[back to top]

Number of Participants With Serious and Non-Serious Adverse Events

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01479348)
Timeframe: Date treatment consent signed to date off study, approximately 20 months and 12 days.

Intervention	Participants (Count of Participants)
1/Intravenous (IV) Tetrahydrouridine (THU)	2

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Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

[F-18]-5-fluoro-2'-deoxycytidine (FdCyd) was administered intravenously with administration of tetrahydrouridine (THU) and the frequency and severity of adverse events was observed. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 0 is normal, Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. (NCT01479348)
Timeframe: Within 5 days after interventions

Intervention	adverse events (Number)
	Day 1 Adverse Events	Day 2, Grade 2 Hypoalbuminemia	Day 2, Grade 3 Anemia	Day 3 Adverse Events	Day 4 Adverse Events	Day 5 Adverse Events
1/Intravenous (IV) Tetrahydrouridine (THU)	0	1	1	0	0	0

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Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans

Radiation dosimetry was determined based on the first patients. This involved making region of interest measurements on the scan for each major organ and measuring the uptake. Using standard dosimetry software this is converted into mSv/MBq, a standard measure of dosimetry. The software is known as Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA) and is commonly used to generate this kind of data. (NCT01479348)
Timeframe: 1 year

Intervention	mSv/MBq (Mean)
	Adrenals	Brain	Breasts	Gallbladder wall	Lower large intestine wall	Small intestine	Stomach wall	Upper large intestine wall	Heart wall	Kidneys	Liver	Lungs	Muscle	Ovaries	Pancreas	Red marrow	Osteogenic cells	Skin	Spleen	Testes	Thymus	Thyroid	Urinary bladder wall	Uterus
1/Intravenous (IV) Tetrahydrouridine (THU)	1.83	8.17	1.03	4.05	2.52	2.13	1.90	2.04	1.10	5.26	6.02	1.82	1.16	1.57	1.63	1.14	1.71	8.65	1.69	1.03	1.12	8.23	7.96	1.63

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Tumor to Background Ratios (TBRs) of Target Lesions at 4 Time Points After Injection

Participants were scanned by positron emission tomography (PET) and lesions were measured at 4 time points after injection. (NCT01479348)
Timeframe: 9 minutes, 32 minutes, 56 minutes and 2 hours after injection

Intervention	TBR ratio (Number)
	Pt 1 L. Parotid adenosquam. cell ca at 9 min	Pt 1 L. Parotid adenosquam. cell ca at 32 min	Pt 1 L. Parotid adenosquam. cell ca at 56 min	Pt 1 L. Parotid adenosquam. cell ca at 2 hrs	Pt 2 R. Parapharyngeal Spindle Cell Ca at 9 min	Pt 2 R. Parapharyngeal Spindle Cell Ca at 32 min	Pt 2 R. Parapharyngeal Spindle Cell Ca at 56 min	Pt 2 R. Parapharyngeal Spindle Cell Ca at 2 hrs	Pt 3 Non-small Cell Lung Ca at 9 min	Pt 3 Non-small Cell Lung Ca at 32 min	Pt 3 Non-small Cell Lung Ca at 56 min	Pt 3 Non-small Cell Lung Ca at 2 hrs	Pt 4 Non-small Cell Lung Ca at 9 min	Pt 4 Non-small Cell Lung Ca at 32 min	Pt 4 Non-small Cell Lung Ca at 56 min	Pt 4 Non-small Cell Lung Ca at 2 hrs	Pt 5 Hepatocellular Ca at 9 min	Pt 5 Hepatocellular Ca at 32 min	Pt 5 Hepatocellular Ca at 56 min	Pt 5 Hepatocellular Ca at 2 hrs
1/Intravenous (IV) Tetrahydrouridine (THU)	1.4	1.5	1.5	1.6	1.9	1.7	1.7	1.6	1.4	1.4	1.5	1.7	2.4	2.1	1.6	2.0	NA	NA	NA	NA

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Overall Survival

Overall survival: It is defined as the time from randomization to the date of death. A subject who has not died will be censored at last known date alive. Overall survival (OS) will be followed continuously while subjects are on the study drug. (NCT02664181)
Timeframe: Up to 171 weeks after beginning treatment

Intervention	Days (Median)
Nivolumab	844
Oral THU/Decitabine + Nivolumab	389.5

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Time-to-Progression

Time-to-Progression defined as the time from randomization to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Subjects who die without a reported prior progression will be considered to have progressed on the date of their death. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment. Subjects who did not have any on study tumor assessments and did not die will be censored on the date they were randomized. Subjects who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to initiation of the subsequent anti-cancer therapy. Progression will be assessed every 6 weeks (from the first on-study radiographic assessment) until disease progression is noted. (NCT02664181)
Timeframe: Up to 77 weeks after beginning treatment

Intervention	days (Median)
Nivolumab	227
Oral THU/Decitabine + Nivolumab	69

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Maximum Tolerated Dose (MTD) of Decitabine

Maximum Tolerated Dose (MTD) is the maximum dose at which fewer than one-third of participants experience dose limiting toxicity (DLT) within the first 6 weeks (two cycles) of decitabine and tetrahydrouridine therapy. If one of three patients at any given dose level experiences DLT, up to three additional patients will be treated at this dose level. If only one of six patients exhibit DLT, subsequent patients will be enrolled into the next higher dose level. As soon as two patients at any given dose level develop DLT, no additional patients will be entered at that level. Subsequent patients will be accrued into the preceding dose level; if DLT is observed in less than two of six patients treated at this lower level, this dose will represent maximum tolerated dose (MTD). A DLT is any Grade 3 or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness. (NCT03233724)
Timeframe: Within the first 6 weeks (two cycles)

Intervention	mg/kg (Number)
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)	NA
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)	NA
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks	NA

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Maximum Tolerated Dose (MTD) of Tetrahydrouridine

Intervention	mg/kg (Number)
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)	NA
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)	NA
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks	NA

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Number of Participants With a Dose Limiting Hematologic Toxicity (DLT)

A DLT is any Grade 3 (severe) or greater toxicity that cannot be attributed to a cause other than study treatment during the first two cycles of Course 1 of therapy such as disease progression or intercurrent illness. (NCT03233724)
Timeframe: First two cycles of Course 1 of therapy

Intervention	Participants (Count of Participants)
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)	2
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)	2
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks	1

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Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT03233724)
Timeframe: Date treatment consent signed to date off study, approximately 2 months/10 days, 10 months/29 days, 20 months/30 days for the first, second and third group respectively.

Intervention	Participants (Count of Participants)
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)	2
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)	2
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks	4

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Overall Response Rate

Overall response rate was measured using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine if the combination of decitabine and tetrahydrouridine is associated with a response rate which exceeds that of Pembrolizumab alone in participants who have programmed death-ligand 1 (PD-L1) expression of at least 50% and those who do not. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions. (NCT03233724)
Timeframe: Every 10 weeks (± 1 week) until disease progression or unacceptable toxicity or off study criteria is met. Longest participant on study 11 months.

Intervention	Participants (Count of Participants)
	Complete Response	Partial Response	Stable Disease	Progressive Disease	Unevaluable for response
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Every (q) Tuesday,Wednesday (TW) x 2 Weeks q3Weeks	0	0	1	1	2
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Monday-Tuesday (MT)	0	0	0	1	1
Decitabine 0.2mg/kg + Tetrahydrouridine 10mg/kg Sunday, Monday, Tuesday (SuMT)	0	0	0	0	2

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Substance	Relationship Strength	Studies	Trials	Classes	Roles
adenine [no description available]	3.05	1	0	6-aminopurines; purine nucleobase	Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
methane Methane: The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed). methane : A one-carbon compound in which the carbon is attached by single bonds to four hydrogen atoms. It is a colourless, odourless, non-toxic but flammable gas (b.p. -161degreeC).	3.42	1	1	alkane; gas molecular entity; mononuclear parent hydride; one-carbon compound	bacterial metabolite; fossil fuel; greenhouse gas
salicylic acid Scalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).	1.96	1	0	monohydroxybenzoic acid	algal metabolite; antifungal agent; antiinfective agent; EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor; keratolytic drug; plant hormone; plant metabolite
3-hydroxybutyric acid 3-Hydroxybutyric Acid: BUTYRIC ACID substituted in the beta or 3 position. It is one of the ketone bodies produced in the liver.. 3-hydroxybutyric acid : A straight-chain 3-hydroxy monocarboxylic acid comprising a butyric acid core with a single hydroxy substituent in the 3- position; a ketone body whose levels are raised during ketosis, used as an energy source by the brain during fasting in humans. Also used to synthesise biodegradable plastics.	3.42	1	1	(omega-1)-hydroxy fatty acid; 3-hydroxy monocarboxylic acid; hydroxybutyric acid	human metabolite
phosphonoacetic acid Phosphonoacetic Acid: A simple organophosphorus compound that inhibits DNA polymerase, especially in viruses and is used as an antiviral agent.. phosphonoacetic acid : A member of the class of phosphonic acids that is phosphonic acid in which the hydrogen attached to the phosphorous is replaced by a carboxymethyl group.	2.89	4	0	monocarboxylic acid; phosphonic acids	antiviral agent; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor
cytosine [no description available]	2.43	2	0	aminopyrimidine; pyrimidine nucleobase; pyrimidone	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
dihydroxyphenylalanine Dihydroxyphenylalanine: A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.. dopa : A hydroxyphenylalanine carrying hydroxy substituents at positions 3 and 4 of the benzene ring.	3.42	1	1	hydroxyphenylalanine; non-proteinogenic alpha-amino acid; tyrosine derivative	human metabolite
uracil 2,4-dihydroxypyrimidine: a urinary biomarker for bipolar disorder	4.61	6	1	pyrimidine nucleobase; pyrimidone	allergen; Daphnia magna metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; prodrug; Saccharomyces cerevisiae metabolite
acetazolamide Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)	3.42	1	1	monocarboxylic acid amide; sulfonamide; thiadiazoles	anticonvulsant; diuretic; EC 4.2.1.1 (carbonic anhydrase) inhibitor
fluorouracil Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.	9.89	8	1	nucleobase analogue; organofluorine compound	antimetabolite; antineoplastic agent; environmental contaminant; immunosuppressive agent; radiosensitizing agent; xenobiotic
hydroxyurea [no description available]	1.97	1	0	one-carbon compound; ureas	antimetabolite; antimitotic; antineoplastic agent; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; genotoxin; immunomodulator; radical scavenger; teratogenic agent
thymidine [no description available]	5.38	7	0	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; metabolite; mouse metabolite
floxuridine Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.. floxuridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.	4.46	5	1	nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; radiosensitizing agent
idoxuridine [no description available]	3.76	3	0	organoiodine compound; pyrimidine 2'-deoxyribonucleoside	antiviral drug; DNA synthesis inhibitor
aspartic acid Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.. aspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent. L-aspartic acid : The L-enantiomer of aspartic acid.	2.89	4	0	aspartate family amino acid; aspartic acid; L-alpha-amino acid; proteinogenic amino acid	Escherichia coli metabolite; mouse metabolite; neurotransmitter
cyanides Cyanides: Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical.. cyanides : Salts and C-organyl derivatives of hydrogen cyanide, HC#N.. isocyanide : The isomer HN(+)#C(-) of hydrocyanic acid, HC#N, and its hydrocarbyl derivatives RNC (RN(+)#C(-)).. cyanide : A pseudohalide anion that is the conjugate base of hydrogen cyanide.	1.95	1	0	pseudohalide anion	EC 1.9.3.1 (cytochrome c oxidase) inhibitor
uridine [no description available]	7.15	35	3	uridines	drug metabolite; fundamental metabolite; human metabolite
bromodeoxyuridine Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.	2.66	3	0	pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent
edetic acid Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.	3.42	1	1	ethylenediamine derivative; polyamino carboxylic acid; tetracarboxylic acid	anticoagulant; antidote; chelator; copper chelator; geroprotector
adenosine monophosphate Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.	3.05	1	0	adenosine 5'-phosphate; purine ribonucleoside 5'-monophosphate	adenosine A1 receptor agonist; cofactor; EC 3.1.3.1 (alkaline phosphatase) inhibitor; EC 3.1.3.11 (fructose-bisphosphatase) inhibitor; fundamental metabolite; micronutrient; nutraceutical
cytidine diphosphate Cytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate.	1.97	1	0	cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-diphosphate	Escherichia coli metabolite; mouse metabolite
cytidine [no description available]	3.58	9	0	cytidines	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
cytidine triphosphate Cytidine Triphosphate: Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety.	1.97	1	0	cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-triphosphate	Escherichia coli metabolite; mouse metabolite
cytarabine [no description available]	8.41	35	2	beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside	antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent
trifluridine Trifluridine: An antiviral derivative of THYMIDINE used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to HERPES SIMPLEX virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557). trifluridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-trifluoromethyluracil as the nucleobase. An antiviral drug used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis.	1.96	1	0	nucleoside analogue; organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; EC 2.1.1.45 (thymidylate synthase) inhibitor
methyl acrylate [no description available]	3.42	1	1	enoate ester
5-fluorouridine [no description available]	3.43	1	1	organofluorine compound; uridines	mutagen
azacitidine Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.	6.99	16	2	N-glycosyl-1,3,5-triazine; nucleoside analogue	antineoplastic agent
deoxycytidine [no description available]	10.08	54	5	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
deoxyuridine [no description available]	3.25	6	0	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
deoxycytidine monophosphate Deoxycytidine Monophosphate: Deoxycytidine (dihydrogen phosphate). A deoxycytosine nucleotide containing one phosphate group esterified to the deoxyribose moiety in the 2'-,3'- or 5- positions.. 2'-deoxycytosine 5'-monophosphate : A pyrimidine 2'-deoxyribonucleoside 5'-monophosphate having cytosine as the nucleobase.	3.34	2	0	2'-deoxycytidine phosphate; pyrimidine 2'-deoxyribonucleoside 5'-monophosphate	Escherichia coli metabolite; mouse metabolite
tetrachloroisophthalonitrile tetrachloroisophthalonitrile: structure. chlorothalonil : A dinitrile that is benzene-1,3-dicarbonitrile substituted by four chloro groups. A non-systemic fungicide first introduced in the 1960s, it is used to control a range of diseases in a wide variety of crops.	3.42	1	1	aromatic fungicide; dinitrile; tetrachlorobenzene	antifungal agrochemical
stavudine Stavudine: A dideoxynucleoside analog that inhibits reverse transcriptase and has in vitro activity against HIV.. stavudine : A nucleoside analogue obtained by formal dehydration across positions 2 and 3 of thymidine. An inhibitor of HIV-1 reverse transcriptase	2.01	1	0	dihydrofuran; nucleoside analogue; organic molecular entity	antimetabolite; antiviral agent; EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
vidarabine adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond.	3.47	2	0	beta-D-arabinoside; purine nucleoside	antineoplastic agent; bacterial metabolite; nucleoside antibiotic
mercury Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.. mercury(0) : Elemental mercury of oxidation state zero.	3.42	1	1	elemental mercury; zinc group element atom	neurotoxin
titanium Titanium: A dark-gray, metallic element of widespread distribution but occurring in small amounts with atomic number, 22, atomic weight, 47.867 and symbol, Ti; specific gravity, 4.5; used for fixation of fractures.	3.42	1	1	titanium group element atom
cadmium Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.. elemental cadmium : An element in the zinc group of the periodic table with atomic number 48, atomic mass 112, M.P. 321degreeC, and B.P. 765degreeC). An odourless, tasteless, and highly poisonous soft, ductile, lustrous metal with electropositive properties. It has eight stable isotopes: (106)Cd, (108)Cd,(110)Cd, (111)Cd, (112)Cd, (113)Cd, (114)Cd and (116)Cd, with (112)Cd and (114)Cd being the most common.	3.42	1	1	cadmium molecular entity; zinc group element atom
zalcitabine Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy.. zalcitabine : A pyrimidine 2',3'-dideoxyribonucleoside compound having cytosine as the nucleobase.	2.67	3	0	pyrimidine 2',3'-dideoxyribonucleoside	antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor
copper sulfate Copper Sulfate: A sulfate salt of copper. It is a potent emetic and is used as an antidote for poisoning by phosphorus. It also can be used to prevent the growth of algae.. copper(II) sulfate : A metal sulfate compound having copper(2+) as the metal ion.	3.42	1	1	metal sulfate	emetic; fertilizer; sensitiser
fluorine Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as fluoride (FLUORIDES) to prevent dental caries.	2.1	1	0	diatomic fluorine; gas molecular entity	NMR chemical shift reference compound
coformycin [no description available]	2.03	1	0	coformycins	EC 3.5.4.4 (adenosine deaminase) inhibitor
arabinofuranosylcytosine triphosphate Arabinofuranosylcytosine Triphosphate: A triphosphate nucleotide analog which is the biologically active form of CYTARABINE. It inhibits nuclear DNA synthesis.	3.06	5	0
zidovudine Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.. zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.	2.4	2	0	azide; pyrimidine 2',3'-dideoxyribonucleoside	antimetabolite; antiviral drug; HIV-1 reverse transcriptase inhibitor
fiacitabine fiacitabine: anti-herpes virus agent which also inhibits growth of certain human tumor cell lines in vitro.	1.96	1	0
5-benzylacyclouridine 5-benzylacyclouridine: structure given in first source. 5-benzyl-1-(2-hydroxyethoxymethyl)uracil : A pyrimidone that is uracil which is substituted by a 2-hydroxyethoxymethyl group at position 1 and a benzyl group at position 5.	2.37	2	0	hydroxyether; primary alcohol; pyrimidone
gemcitabine gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.	3.64	9	0	organofluorine compound; pyrimidine 2'-deoxyribonucleoside	antimetabolite; antineoplastic agent; antiviral drug; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; environmental contaminant; immunosuppressive agent; photosensitizing agent; prodrug; radiosensitizing agent; xenobiotic
capecitabine Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.	2.45	2	0	carbamate ester; cytidines; organofluorine compound	antimetabolite; antineoplastic agent; prodrug
2',3'-dideoxycytidinene 2',3'-dideoxycytidinene: 2',3'-unsaturated derivative of 2',3'-dideoxycytidine; potent inhibitor of HTLV-III in vitro; structure given in first source	1.97	1	0
thymidine 5'-triphosphate thymidine 5'-triphosphate: RN given refers to parent cpd. dTTP : A thymidine phosphate having a triphosphate group at the 5'-position.	2.39	2	0	pyrimidine 2'-deoxyribonucleoside 5'-triphosphate; thymidine phosphate	Escherichia coli metabolite; mouse metabolite
5-methylcytosine 5-Methylcytosine: A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.. 5-methylcytosine : A pyrimidine that is a derivative of cytosine, having a methyl group at the 5-position.	1.97	1	0	methylcytosine; pyrimidines	human metabolite
2'-deoxycytidine 5'-triphosphate 2'-deoxycytidine 5'-triphosphate: RN given refers to unlabeled parent cpd	2.89	4	0	2'-deoxycytidine phosphate; pyrimidine 2'-deoxyribonucleoside 5'-triphosphate	Escherichia coli metabolite; human metabolite; mouse metabolite
5,6-dihydro-5-azacytidine 5,6-dihydro-5-azacytidine: NSC-264880 refers to 5,6-dihydro-5-azacytidine hydrochloride	1.95	1	0
pyrimidin-2-one beta-ribofuranoside pyrimidin-2-one beta-ribofuranoside: RN given refers to (D)-isomer; structure	2.43	2	0	pyrimidine ribonucleosides
5-chloro-2'-deoxycytidine [no description available]	8.48	8	0
deoxy-5-methylcytidylic acid 2'-deoxy-5-methyl-5'-cytidylic acid : A pyrimidine 2'-deoxyribonucleoside 5'-monophosphate having 5-methylcytidine as the nucleobase.	1.97	1	0	2'-deoxycytidine phosphate; pyrimidine 2'-deoxyribonucleoside 5'-monophosphate
cobalt Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.. cobalt(1+) : A monovalent inorganic cation obtained from cobalt.. cobalt atom : A cobalt group element atom that has atomic number 27.	3.42	1	1	cobalt group element atom; metal allergen	micronutrient
5-fluoropyrimidin-2-one beta-ribofuranoside [no description available]	1.98	1	0
carboplatin [no description available]	6.98	1	0
5-methyldeoxycytidine [no description available]	1.96	1	0	2'-deoxycytidine
tretinoin Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).. all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry.	1.97	1	0	retinoic acid; vitamin A	anti-inflammatory agent; antineoplastic agent; antioxidant; AP-1 antagonist; human metabolite; keratolytic drug; retinoic acid receptor agonist; retinoid X receptor agonist; signalling molecule
resveratrol trans-resveratrol : A resveratrol in which the double bond has E configuration.	3.42	1	1	resveratrol	antioxidant; phytoalexin; plant metabolite; quorum sensing inhibitor; radical scavenger
brivudine brivudine: anti-herpes agent	1.97	1	0
decitabine [no description available]	6.85	13	2	2'-deoxyribonucleoside
bromodeoxycytidine Bromodeoxycytidine: 5-Bromo-2'-deoxycytidine. Can be incorporated into DNA in the presence of DNA polymerase, replacing dCTP.	1.97	1	0
5-fluoro-2'-deoxycytidine 5-fluoro-2'-deoxycytidine: structure	7.49	14	4
isomethyleugenol Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)	2.37	2	0	isomethyleugenol
floxuridine [no description available]	2.13	1	0
mercaptopurine Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.. purine-6-thiol : A thiol that is the tautomer of mercaptopurine.. mercaptopurine : A member of the class of purines that is 6,7-dihydro-1H-purine carrying a thione group at position 6. An adenine analogue, it is used in the treatment of acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), Crohn's disease, and ulcerative colitis.	1.98	1	0	aryl thiol; purines; thiocarbonyl compound	anticoronaviral agent; antimetabolite; antineoplastic agent
cobaltous chloride cobaltous chloride: RN given refers to unlabeled cpd; RN in Chemline for cobalt trichloride: 10241-04-0; RN for 60-labeled cpd: 14543-09-0; RN for 57-labeled cpd: 164113-89-1; RN for 58-labeled cpd: 29377-09-1; structure. cobalt dichloride : A cobalt salt in which the cobalt metal is in the +2 oxidation state and the counter-anion is chloride. It is used as an indicator for water in desiccants.	3.42	1	1	cobalt salt; inorganic chloride	allergen; calcium channel blocker; sensitiser; two-colour indicator
ubiquinone 9 ubiquinone 9: a form of coenzyme Q found in many foods; RN given refers to (all-E)-isomer	3.42	1	1	ubiquinones	antioxidant; human metabolite
alprostadil [no description available]	1.96	1	0	prostaglandins E	anticoagulant; human metabolite; platelet aggregation inhibitor; vasodilator agent
phosphorus Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.	1.95	1	0	monoatomic phosphorus; nonmetal atom; pnictogen	macronutrient
arabinofuranosyluracil Arabinofuranosyluracil: A pyrimidine nucleoside formed in the body by the deamination of CYTARABINE.	2.65	3	0
aflatoxin m1 Aflatoxin M1: A 4-hydroxylated metabolite of AFLATOXIN B1, one of the MYCOTOXINS from ASPERGILLUS tainted food. It is associated with LIVER damage and cancer resulting from its P450 activation to the epoxide which alkylates DNA. Toxicity depends on the balance of liver enzymes that activate it (CYTOCHROME P-450) and others that detoxify it (GLUTATHIONE S TRANSFERASE) (Pharmac Ther 50.443 1991). Primates & rat are sensitive while mouse and hamster are tolerant (Canc Res 29.236 1969).. aflatoxin M1 : A member of the class of aflatoxins that is aflatoxin B1 in which the hydrogen at position 9a is replaced by a hydroxy group.	3.42	1	1	aflatoxin; aromatic ether; aromatic ketone; tertiary alcohol	Aspergillus metabolite; human xenobiotic metabolite; mammalian metabolite
glycoprotein e2, hepatitis c virus glycoprotein E2, Hepatitis C virus: RN refers to quasispecies 4E; amino acid sequence known; caution: HCV also stands for hog cholera virus	3.42	1	1
ubiquinone Ubiquinone: A lipid-soluble benzoquinone which is involved in ELECTRON TRANSPORT in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals.	3.42	1	1
salicylates Salicylates: The salts or esters of salicylic acids, or salicylate esters of an organic acid. Some of these have analgesic, antipyretic, and anti-inflammatory activities by inhibiting prostaglandin synthesis.. hydroxybenzoate : Any benzoate derivative carrying a single carboxylate group and at least one hydroxy substituent.. salicylates : Any salt or ester arising from reaction of the carboxy group of salicylic acid, or any ester resulting from the condensation of the phenolic hydroxy group of salicylic acid with an organic acid.. salicylate : A monohydroxybenzoate that is the conjugate base of salicylic acid.	1.96	1	0	monohydroxybenzoate	plant metabolite
3-deazauridine 3-Deazauridine: 4-Hydroxy-1-(beta-D-ribofuranosyl)-2-pyridinone. Analog of uridine lacking a ring-nitrogen in the 3-position. Functions as an antineoplastic agent.	2.66	3	0	N-glycosyl compound
praliciguat praliciguat: soluble guanylate cyclase stimulator. praliciguat : A member of the class of pyrazoles that is 5-fluoro-2-(1H-pyrazol-3-yl)pyrimidine which is substituted by a 2-fluorobenzyl group at position 1, 1,2-oxazol-3-yl group at position 5, and by a [3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propyl]nitrilo group at position 4. It is a soluble guanylate cyclase stimulator under clinical development for the treatment of heart failure with preserved ejection fraction.	3.42	1	1	aminopyrimidine; isoxazoles; monofluorobenzenes; organofluorine compound; pyrazoles; secondary amino compound; tertiary alcohol	anti-inflammatory agent; antihypertensive agent; soluble guanylate cyclase activator; vasodilator agent
deoxyguanosine [no description available]	2.66	3	0	purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
deoxyinosine [no description available]	2.03	1	0	purine 2'-deoxyribonucleoside; purines 2'-deoxy-D-ribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; plant metabolite; Saccharomyces cerevisiae metabolite
guanine [no description available]	1.96	1	0	2-aminopurines; oxopurine; purine nucleobase	algal metabolite; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
guanosine ribonucleoside : Any nucleoside where the sugar component is D-ribose.	1.95	1	0	guanosines; purines D-ribonucleoside	fundamental metabolite
inosine [no description available]	2.03	1	0	inosines; purines D-ribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
pyrimidinones Pyrimidinones: Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O.	1.96	1	0

Condition	Relationship Strength	Studies	Trials
Breast Cancer [description not available]	6.2	9	4
Breast Neoplasms Tumors or cancer of the human BREAST.	6.2	9	4
Adenocarcinoma, Basal Cell [description not available]	3.23	6	0
Colorectal Cancer [description not available]	2.52	2	0
Adenocarcinoma A malignant epithelial tumor with a glandular organization.	3.23	6	0
Colorectal Neoplasms Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.	2.52	2	0
Eperythrozoonosis [description not available]	2.59	2	0
Benign Neoplasms [description not available]	5.79	8	3
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	5.79	8	3
Gastric Outlet Obstruction The hindering of output from the STOMACH into the SMALL INTESTINE. This obstruction may be of mechanical or functional origin such as EDEMA from PEPTIC ULCER; NEOPLASMS; FOREIGN BODIES; or AGING.	3.42	1	1
Cardiometabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY.	3.42	1	1
Fatty Liver, Nonalcoholic [description not available]	3.42	1	1
Cancer of Colon [description not available]	3.78	2	1
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	5.42	5	1
Glial Cell Tumors [description not available]	3.77	2	1
Cancer of Liver [description not available]	3.84	2	1
Infections, Plasmodium [description not available]	3.42	1	1
Cells, Neoplasm Circulating [description not available]	3.42	1	1
Morbid Obesity [description not available]	5.51	4	4
Cancer of Pancreas [description not available]	4.13	3	1
Complication, Postoperative [description not available]	5.51	4	4
Cancer of Prostate [description not available]	5.69	5	4
Cancer of Stomach [description not available]	5.51	4	4
Leanness [description not available]	3.42	1	1
Thrombopenia [description not available]	3.42	1	1
Cancer of the Urinary Tract [description not available]	3.42	1	1
Infections, Helicobacter [description not available]	3.42	1	1
Anemia, Splenic [description not available]	3.42	1	1
Infection, Postoperative Wound [description not available]	3.42	1	1
Local Neoplasm Recurrence [description not available]	5.51	4	4
Invasiveness, Neoplasm [description not available]	3.42	1	1
Carcinoma, Transitional Cell A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.	3.42	1	1
Colonic Neoplasms Tumors or cancer of the COLON.	3.78	2	1
Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)	3.77	2	1
Liver Neoplasms Tumors or cancer of the LIVER.	3.84	2	1
Malaria A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	3.42	1	1
Obesity A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).	3.42	1	1
Obesity, Morbid The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.	5.51	4	4
Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	4.13	3	1
Postoperative Complications Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.	5.51	4	4
Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.	3.42	1	1
Prostatic Neoplasms Tumors or cancer of the PROSTATE.	5.69	5	4
Stomach Neoplasms Tumors or cancer of the STOMACH.	5.51	4	4
Thrombocytopenia A subnormal level of BLOOD PLATELETS.	3.42	1	1
Helicobacter Infections Infections with organisms of the genus HELICOBACTER, particularly, in humans, HELICOBACTER PYLORI. The clinical manifestations are focused in the stomach, usually the gastric mucosa and antrum, and the upper duodenum. This infection plays a major role in the pathogenesis of type B gastritis and peptic ulcer disease.	3.42	1	1
Metabolic Syndrome A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.	3.42	1	1
Non-alcoholic Fatty Liver Disease Fatty liver finding without excessive ALCOHOL CONSUMPTION.	3.42	1	1
Germinoblastoma [description not available]	4.35	2	2
Lymphoma A general term for various neoplastic diseases of the lymphoid tissue.	4.35	2	2
Electron Transport Chain Deficiencies, Mitochondrial [description not available]	3.06	1	0
Inborn Errors of Metabolism [description not available]	3.06	1	0
Metabolism, Inborn Errors Errors in metabolic processes resulting from inborn genetic mutations that are inherited or acquired in utero.	3.06	1	0
Mitochondrial Diseases Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.	3.06	1	0
HbS Disease [description not available]	4.45	1	1
Anemia, Sickle Cell A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.	4.45	1	1
Experimental Mammary Neoplasms [description not available]	3.07	5	0
Benign Neoplasms, Brain [description not available]	2.13	1	0
Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	2.13	1	0
Sensitivity and Specificity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)	2.45	2	0
B16 Melanoma [description not available]	2.07	1	0
Cancer of Lung [description not available]	3.35	7	0
Lung Neoplasms Tumors or cancer of the LUNG.	3.35	7	0
Granulocytic Leukemia [description not available]	3.98	5	0
Leukemia, Myeloid Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.	3.98	5	0
Carcinoma, Epidermoid [description not available]	2.66	3	0
Cancer of Larynx [description not available]	1.96	1	0
Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	2.66	3	0
Laryngeal Neoplasms Cancers or tumors of the LARYNX or any of its parts: the GLOTTIS; EPIGLOTTIS; LARYNGEAL CARTILAGES; LARYNGEAL MUSCLES; and VOCAL CORDS.	1.96	1	0
Leucocythaemia [description not available]	6.54	6	2
Leukemia, Lymphocytic [description not available]	3.57	3	0
Acute Myelogenous Leukemia [description not available]	3.21	6	0
Leukemia A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)	6.54	6	2
Leukemia, Lymphoid Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.	3.57	3	0
Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.	3.21	6	0
Purine Pyrimidine Metabolism, Inborn Errors [description not available]	1.96	1	0
Amino Acid Metabolism Disorders, Inborn [description not available]	3.35	1	1
Carcinoma, Ehrlich Tumor A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.	1.96	1	0
Leukemia L 1210 [description not available]	3.06	5	0
Experimental Leukemia [description not available]	2.66	3	0
Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.	1.98	1	0
ATLL [description not available]	1.98	1	0
Leukemia-Lymphoma, Adult T-Cell Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.	1.98	1	0
Recrudescence [description not available]	1.98	1	0
Blast Phase [description not available]	1.98	1	0
Granulocytic Leukemia, Chronic [description not available]	1.98	1	0
Acute Disease Disease having a short and relatively severe course.	1.98	1	0
Blast Crisis An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.	6.98	1	0
Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.	1.98	1	0
Astrocytoma, Grade IV [description not available]	2	1	0
Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.	2	1	0
Malignant Melanoma [description not available]	2.36	2	0
Experimental Neoplasms [description not available]	3.21	6	0
Sarcoma 180 An experimental sarcoma of mice.	2.35	2	0
Osteogenic Sarcoma [description not available]	2.35	2	0
Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	7.36	2	0
Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)	2.35	2	0
Cell Transformation, Viral An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.	1.95	1	0
Viral Diseases [description not available]	2.87	1	0
Virus Diseases A general term for diseases caused by viruses.	2.87	1	0
EHS Tumor [description not available]	2.37	2	0
Bone Cancer [description not available]	1.95	1	0
Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES.	1.95	1	0
Acute Promyelocytic Leukemia [description not available]	2.67	3	0
Leukemia, Promyelocytic, Acute An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.	2.67	3	0
Acquired Immune Deficiency Syndrome [description not available]	2.38	2	0
Antibody Deficiency Syndrome [description not available]	2.38	2	0
Infections, Retroviridae [description not available]	1.97	1	0
Viremia The presence of viruses in the blood.	1.97	1	0
Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.	2.38	2	0
Immunologic Deficiency Syndromes Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.	2.38	2	0
Retroviridae Infections Virus diseases caused by the RETROVIRIDAE.	1.97	1	0
Agranulocytosis A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).	1.96	1	0
Experimental Hepatoma [description not available]	1.96	1	0
Hypothermia, Accidental [description not available]	1.97	1	0
Hypothermia Lower than normal body temperature, especially in warm-blooded animals.	1.97	1	0

tetrahydrouridine

Description

Cross-References

Synonyms (2)

Research Excerpts

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Research

Studies (116)

Study Types

Clinical Trials (17)

Trial Overview

Trial Outcomes

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).

Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)

Progression-free Survival (PFS)

Number of Participants With Serious and Non-Serious Adverse Events

Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans

Tumor to Background Ratios (TBRs) of Target Lesions at 4 Time Points After Injection

Overall Survival

Time-to-Progression

Maximum Tolerated Dose (MTD) of Decitabine

Maximum Tolerated Dose (MTD) of Tetrahydrouridine

Number of Participants With a Dose Limiting Hematologic Toxicity (DLT)

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Response Rate

tetrahydrouridine

Description

Cross-References

Synonyms (2)

Research Excerpts

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Research

Studies (116)

Study Types

Clinical Trials (17)

Trial Overview

Trial Outcomes

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0).

Percentage of Participants With (Complete Response (CR) + Partial Response (PR)) to 5-Fluro-2'-Deoxycytidine (FdCyd)

Progression-free Survival (PFS)

Number of Participants With Serious and Non-Serious Adverse Events

Frequency and Severity of Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0

Radiation Dosimetry Estimates of 5-fluoro-2'-Deoxycytidine (FdCyd) in Humans

Tumor to Background Ratios (TBRs) of Target Lesions at 4 Time Points After Injection

Overall Survival

Time-to-Progression

Maximum Tolerated Dose (MTD) of Decitabine

Maximum Tolerated Dose (MTD) of Tetrahydrouridine

Number of Participants With a Dose Limiting Hematologic Toxicity (DLT)

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Overall Response Rate

Related Drugs (85)

Related Conditions (115)