Page last updated: 2024-12-11

pr-104a

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

PR-104A: 3,5-dinitrobenzamide nitrogen mustard, an alkyating antineoplastic; PR-104A is the corresponding alcohol of PR104 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9848786
CHEMBL ID4438907
SCHEMBL ID366334
MeSH IDM0515481

Synonyms (23)

Synonym
680199-06-8
pr-104a
SCHEMBL366334
AZICEEZSDKZDHX-UHFFFAOYSA-N
2-((2-bromoethyl)-2-{[(2-hydroxyethyl)amino]carbonyl}-4,6-dinitroanilino)ethyl methanesulfonate
AKOS025147034
397986RF9L ,
3,5-dinitrobenzamide nitrogen mustard
2-(n-(2-bromoethyl)-2-(((2-hydroxyethyl)amino)carbonyl)-4,6-dinitroanilino)ethyl methanesulfonate
benzamide, 2-((2-bromoethyl)(2-((methylsulfonyl)oxy)ethyl)amino)-n-(2-hydroxyethyl)-3,5-dinitro-
2-((2-bromoethyl)(2-((methylsulfonyl)oxy)ethyl)amino)-n-(2-hydroxyethyl)-3,5-dinitrobenzamide
2-((2-bromoethyl)(2-((2-hydroxyethyl)carbamoyl)-4,6-dinitrophenyl)amino)ethyl methanesulfonate
J-505203
2-[n-(2-bromoethyl)-2-(2-hydroxyethylcarbamoyl)-4,6-dinitroanilino]ethyl methanesulfonate
pr 104a
unii-397986rf9l
sn 27858
MS-29270
CHEMBL4438907
HY-14572
CS-0003452
2-((2-bromoethyl)(2-((2-hydroxyethyl)carbamoyl)-4,6-dinitrophenyl)amino)ethylmethanesulfonate
AKOS040749231

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" Here, we report a population pharmacokinetic (PK) model for PR-104 and PR-104A in non-human species and in humans."( A combined pharmacokinetic model for the hypoxia-targeted prodrug PR-104A in humans, dogs, rats and mice predicts species differences in clearance and toxicity.
Choy, SS; Hicks, KO; Holford, NH; Melink, TJ; Patel, K; Wilson, WR, 2011
)
0.84

Compound-Compound Interactions

ExcerptReferenceRelevance
"The purpose of this phase Ib clinical trial was to determine the maximum tolerated dose (MTD) of PR-104 a bioreductive pre-prodrug given in combination with gemcitabine or docetaxel in patients with advanced solid tumours."( PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours.
Gu, Y; Jameson, MB; McKeage, MJ; Melink, TJ; Rajendran, J; Ramanathan, RK; Tchekmedyian, NS; Wilson, WR, 2012
)
0.38
"PR-104 was administered as a one-hour intravenous infusion combined with docetaxel 60 to 75 mg/m2 on day one given with or without granulocyte colony stimulating factor (G-CSF) on day two or administrated with gemcitabine 800 mg/m2 on days one and eight, of a 21-day treatment cycle."( PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours.
Gu, Y; Jameson, MB; McKeage, MJ; Melink, TJ; Rajendran, J; Ramanathan, RK; Tchekmedyian, NS; Wilson, WR, 2012
)
0.38
" The MTD of PR-104 was 140 mg/m2 when combined with gemcitabine, 200 mg/m2 when combined with docetaxel 60 mg/m2, 770 mg/m2 when combined with docetaxel 60 mg/m2 plus G-CSF and ≥770 mg/m2 when combined with docetaxel 75 mg/m2 plus G-CSF."( PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours.
Gu, Y; Jameson, MB; McKeage, MJ; Melink, TJ; Rajendran, J; Ramanathan, RK; Tchekmedyian, NS; Wilson, WR, 2012
)
0.38
" A recommended dose was identified for phase II trials of PR-104 of 770 mg/m2 combined with docetaxel 60 to 75 mg/m2 both given on day one of a 21-day treatment cycle supported by prophylactic G-CSF (NCT00459836)."( PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours.
Gu, Y; Jameson, MB; McKeage, MJ; Melink, TJ; Rajendran, J; Ramanathan, RK; Tchekmedyian, NS; Wilson, WR, 2012
)
0.38
" PR-104 monotherapy elicited significant reductions in growth of Hep3B and HepG2 xenografts, and the combination with sorafenib was significantly active in all 4 xenograft models."( Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma.
Abbattista, MR; Gu, Y; Guise, CP; Jamieson, SM; Nickel, JE; Patterson, AV; Pullen, SM; Wilson, WR, 2015
)
0.42

Dosage Studied

ExcerptRelevanceReference
") dosing of humans, Beagle dogs, Sprague-Dawley rats and CD-1 nude mice."( A combined pharmacokinetic model for the hypoxia-targeted prodrug PR-104A in humans, dogs, rats and mice predicts species differences in clearance and toxicity.
Choy, SS; Hicks, KO; Holford, NH; Melink, TJ; Patel, K; Wilson, WR, 2011
)
0.61
" At 270 mg/kg and lower dose levels, PR-104 did not induce solid tumor regressions, suggesting a steep dose-response relationship."( Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric preclinical testing program.
Carol, H; Gorlick, R; Gu, Y; Houghton, PJ; Kang, MH; Keir, ST; Kolb, EA; Lock, R; Maris, JM; Morton, CL; Phelps, D; Reynolds, CP; Smith, MA; Wilson, WR; Wozniak, AW, 2011
)
0.37
" PR-104 given weekly may be a suitable protocol for further clinical evaluation as a short course of treatment with fractionated radiotherapy or haematopoietic stem cell support, as its duration of dosing is restricted by delayed-onset and protracted thrombocytopenia."( A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients.
Amies, K; Gu, Y; Hill, A; Jameson, MB; McKeage, MJ; Melink, TJ; Wilson, WR, 2011
)
0.6
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (1)

Processvia Protein(s)Taxonomy
2,4,6-trinitrotoluene catabolic processOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
2,4,6-trinitrotoluene catabolic processOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
NAD(P)H dehydrogenase (quinone) activityOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
6,7-dihydropteridine reductase activityOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
FMN bindingOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
oxidoreductase activityOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
identical protein bindingOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
protein homodimerization activityOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
oxidoreductase activity, acting on other nitrogenous compounds as donors, with NAD or NADP as acceptorOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
cytosolOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
membraneOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
cytosolOxygen-insensitive NAD(P)H nitroreductaseEscherichia coli K-12
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (20)

Assay IDTitleYearJournalArticle
AID1683168Selectivity index, ratio of IC50 for human DU145 cells under normoxic condition to IC50 human PC-3 cells under hypoxia condition incubated for 2 hrs followed by washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1683173Lipophilicity, logD of compound at pH 7.4 by microscale shake flask method2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1683169Cytotoxicity against human DU145 cells assessed as reduction in cell viability incubated for 2 hrs under hypoxic condition followed washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1683170Cytotoxicity against human DU145 cells assessed as reduction in cell viability incubated for 2 hrs under normoxic condition followed by washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1581891Substrate activity at Escherichia coli nitroreductase nfsB assessed as ratio of Kcat/Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method based Michaelis-Menten plot analysis relative to CB1954/NfsB2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1683172Cytotoxicity against human PC-3 cells assessed as reduction in cell viability incubated for 2 hrs under hypoxic condition followed by washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1581890Substrate activity at Escherichia coli nitroreductase nfsA assessed as ratio of Kcat/Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method based Michaelis-Menten plot analysis relative to CB1954/NfsB2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1683167Selectivity index, ratio of IC50 for human PC-3 cells under normoxic condition to IC50 human PC-3 cells under hypoxia condition incubated for 2 hrs followed by washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1595314Substrate activity at Escherichia coli nitroreductase nfsB assessed as Kcat using NADH as cofactor at 0 to 800 mM in Tris-Cl buffer at pH 7.5 by spectrophotometric method2019European journal of medicinal chemistry, Jun-01, Volume: 171PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.
AID1683166Cytotoxicity against human PC-3 cells assessed as reduction in cell viability preincubated for 4 hrs in hypoxia and further incubated for 5 days in fresh medium by SRB assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1683171Cytotoxicity against human PC-3 cells assessed as reduction in cell viability incubated for 2 hrs under normoxic condition followed by washed with fresh media incubated for 3 days by alamar blue assay2021Bioorganic & medicinal chemistry letters, 01-01, Volume: 31Synthesis and evaluation of new dinitrobenzamide mustards in human prostate cancer.
AID1595320Substrate activity at Escherichia coli nitroreductase nfsB assessed as ratio of Kcat/Km up to 80 mM using NADH as cofactor relative to CB1954/NfsB2019European journal of medicinal chemistry, Jun-01, Volume: 171PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.
AID1581877Substrate activity at Escherichia coli nitroreductase nfsB assessed as Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method based Michaelis-Menten plot analysis2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1581869Substrate activity at Escherichia coli nitroreductase nfsA assessed as Kcat using NADPH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1581883Substrate activity at Escherichia coli nitroreductase nfsA assessed as ratio of Kcat/Km using NADPH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometry based Michaelis-Menten plot analysis2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1581876Substrate activity at Escherichia coli nitroreductase nfsA assessed as Km using NADPH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometry based Michaelis-Menten plot analysis2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1595316Substrate activity at Escherichia coli nitroreductase nfsB assessed as ratio of Kcat/Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method2019European journal of medicinal chemistry, Jun-01, Volume: 171PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.
AID1581870Substrate activity at Escherichia coli nitroreductase nfsB assessed as Kcat using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1581884Substrate activity at Escherichia coli nitroreductase nfsB assessed as ratio of Kcat/Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method based Michaelis-Menten plot analysis2020European journal of medicinal chemistry, Feb-01, Volume: 187Prodrugs for nitroreductase-based cancer therapy-3: Antitumor activity of the novel dinitroaniline prodrugs/Ssap-NtrB enzyme suicide gene system: Synthesis, in vitro and in silico evaluation in prostate cancer.
AID1595315Substrate activity at Escherichia coli nitroreductase nfsB assessed as Km using NADH as cofactor in Tris-Cl buffer at pH 7.5 by spectrophotometric method2019European journal of medicinal chemistry, Jun-01, Volume: 171PRODRUGS FOR NITROREDUCTASE BASED CANCER THERAPY- 2: Novel amide/Ntr combinations targeting PC3 cancer cells.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (25)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's4 (16.00)29.6817
2010's18 (72.00)24.3611
2020's3 (12.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 11.59

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index11.59 (24.57)
Research Supply Index3.33 (2.92)
Research Growth Index4.92 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (11.59)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (8.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other23 (92.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]