valopicitabine

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

Description

valopicitabine: prodrug of 2'-C-methylcytidine; an anti-hepatitis C virus agent; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID Source	ID
PubMed CID	6918726
CHEMBL ID	393820
SCHEMBL ID	1378167
MeSH ID	M0492933

Synonyms (21)

Synonym
valopicitabine
val-mcyd
nmc-283
nm-283
CHEMBL393820
[(2r,3r,4r,5r)-5-(4-amino-2-oxo-pyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyl-tetrahydrofuran-3-yl] (2s)-2-amino-3-methyl-butanoate
2'-c-methyl-3'-o-(l-valinyl)-.beta.-d-cytidine
2'-c-methylcytidine 3'-o-valinyl ester
2'-c-methylcytidine 3'-o-l-valinyl ester
i2t0b5g94m ,
l-valine, 3'-ester with 2'-c-methylcytidine
valopicitabine [inn]
unii-i2t0b5g94m
640281-90-9
SCHEMBL1378167
DTXSID70214011
DB13920
HY-108060
CS-0027252
Q27280296
AKOS040740517

Research Excerpts

Pharmacokinetics

Excerpt	Reference	Relevance
" However, pharmacokinetic studies revealed that 2'-C-methylcytidine suffers from a low oral bioavailability."	( Synthesis and pharmacokinetics of valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine. Amador, A; Benzaria, S; Bridges, EG; Cretton-Scott, E; D'Amours, M; Gosselin, G; Mao, J; Mathieu, S; Moussa, A; Pierra, C; Sommadossi, JP; Standring, DN; Storer, R, 2006)	0.61

Bioavailability

Excerpt	Reference	Relevance
"In order to improve the oral bioavailability of 2-C-methylcytidine, a potent anti-HCV agent, the corresponding 3'-O-L-valinyl ester derivative (NM 283) has been synthesized Based on its ease of synthesis and its physicochemical properties, NM 283 has emerged as a promising antiviral drug for treatment of chronic HCV infection."	( Nm 283, an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine. Amador, A; Benzaria, S; Gosselin, G; Mathieu, S; Moussa, A; Pierra, C; Storer, R, 2005)	0.33

Dosage Studied

Excerpt	Relevance	Reference
" Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides."	( Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection. Attenni, B; Di Marco, A; Donghi, M; Fiore, F; Gardelli, C; Gennari, N; Giuliano, C; Harper, S; Laufer, R; Leone, JF; MacCoss, M; Marcucci, I; Meppen, M; Narjes, F; Olsen, DB; Pacini, B; Pucci, V; Rowley, M, 2009)	0.35
" Screening for 2'-C-methylcytidine triphosphate levels in rat liver after oral dosing identified 1-[3,5-difluorophenyl]-1,3-propandiol as an efficient prodrug modification."	( Antiviral efficacy upon administration of a HepDirect prodrug of 2'-C-methylcytidine to hepatitis C virus-infected chimpanzees. Boyer, SH; Carroll, SS; Erion, MD; Fujitaki, JM; Handt, L; Hecker, SJ; Koeplinger, K; Linemeyer, DL; MacCoss, M; Olsen, DB; Reddy, KR; Sun, Z; van Poelje, PD; Vavrek, M; Zhang, NR, 2011)	0.37

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

Bioassays (24)

Assay ID	Title	Year	Journal	Article
AID431942	Stability in cryopreserved primary human hepatocytes assessed as increase in intracellular nucleoside triphosphate formation by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID395002	Metabolic stability in human hepatocyte assessed as nucleoside triphosphate at 10 uM level after 2 hrs	2009	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5	Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
AID431946	Drug concentration in hamster liver assessed as nucleoside triphosphate level at 30.2 umol/kg, po after 6 hrs	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID432340	Cytotoxicity against human HuH7 cells assessed as cell viability	2009	European journal of medicinal chemistry, Sep, Volume: 44, Issue:9	Cyclic phosphoramidates as prodrugs of 2'-C-methylcytidine.
AID431939	Stability in cryopreserved primary human hepatocytes assessed as intracellular nucleoside triphosphate AUC (0 to 4 hrs) at 10 uM by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID299924	Cytotoxicity against Huh7 cells after 24 hrs by MTS assay	2007	Bioorganic & medicinal chemistry, Aug-01, Volume: 15, Issue:15	Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine.
AID431936	Selectivity index, ratio of CC50 for human HBI10A cells to EC50 for HCV infected in human HBI10A cells	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID431938	Stability in human HBI10A cells assessed as intracellular nucleoside triphosphate AUC (0 to 24 hrs) at 100 uM by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID299923	Antiviral activity against HCV genotype 1b in Huh7 cells assessed as inhibition of viral RNA replication after 72 hrs by ribonuclease protection assay	2007	Bioorganic & medicinal chemistry, Aug-01, Volume: 15, Issue:15	Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine.
AID431928	Antiviral activity against HCV assessed as logarithmic reduction in plasma viral RNA at 800 mg, po BID after 14 days	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID431943	Stability in rat hepatocytes assessed as intracellular nucleoside triphosphate AUC (0 to 4 hrs) at 10 uM by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID520334	Antiviral activity against HCV infected in human assessed as log reduction in viral load at 800 mg/kg SID	2008	Antimicrobial agents and chemotherapy, May, Volume: 52, Issue:5	The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors.
AID431933	Antiviral activity against HCV infected in human HBI10A cells by subgenomic viral replicon assay	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID431945	Stability in human hepatocytes assessed as intracellular nucleoside triphosphate AUC (0 to 2 hrs) by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID432331	Antiviral activity against HCV infected in human HuH7 cells by cell-based subgenomic replicon assay	2009	European journal of medicinal chemistry, Sep, Volume: 44, Issue:9	Cyclic phosphoramidates as prodrugs of 2'-C-methylcytidine.
AID395011	Metabolic stability in rat liver assessed as nucleoside triphosphate formation at 30 umol/kg, po after 6 hrs	2009	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5	Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
AID431935	Cytotoxicity against human HBI10A cells	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID395012	Metabolic stability in rat liver assessed as nucleoside triphosphate formation at 1.5 umol/kg, iv after 6 hrs	2009	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5	Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
AID299922	Antiviral activity against HCV genotype 1b in Huh7 cells assessed as inhibition of viral RNA replication after 24 hrs by ribonuclease protection assay	2007	Bioorganic & medicinal chemistry, Aug-01, Volume: 15, Issue:15	Synthesis and HCV inhibitory properties of 9-deaza- and 7,9-dideaza-7-oxa-2'-C-methyladenosine.
AID432332	AUC (0 to 2 hrs) in human hepatocytes assessed as conversion to 2'-C-methylcytidine triphosphate ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate at 10 uM	2009	European journal of medicinal chemistry, Sep, Volume: 44, Issue:9	Cyclic phosphoramidates as prodrugs of 2'-C-methylcytidine.
AID431937	Stability in human HBI10A cells assessed as intracellular nucleoside triphosphate AUC (0 to 24 hrs) at 10 uM by LC-MS/MS analysis	2009	Journal of medicinal chemistry, Sep-10, Volume: 52, Issue:17	Phosphoramidate prodrugs of 2'-C-methylcytidine for therapy of hepatitis C virus infection.
AID432237	Metabolic stability in sc dosed hamster liver assessed as formation of 2'-C-methylcytidine triphosphate ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate at 1.5 umol after 6 hrs	2009	European journal of medicinal chemistry, Sep, Volume: 44, Issue:9	Cyclic phosphoramidates as prodrugs of 2'-C-methylcytidine.
AID395000	Antiviral activity against HCV infected in human hepatoma cells by replicon assay	2009	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5	Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
AID395001	Metabolic stability in rat hepatocyte assessed as nucleoside triphosphate at 10 uM level after 2 hrs	2009	Bioorganic & medicinal chemistry letters, Mar-01, Volume: 19, Issue:5	Synthesis and evaluation of novel phosphoramidate prodrugs of 2'-methyl cytidine as inhibitors of hepatitis C virus NS5B polymerase.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (18)

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	16 (88.89)	29.6817
2010's	2 (11.11)	24.3611
2020's	0 (0.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 18.92

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 moderate demand-to-supply ratio for research on this compound.

Metric	This Compound (vs All)
Research Demand Index	18.92 (24.57)
Research Supply Index	2.94 (2.92)
Research Growth Index	4.23 (4.65)
Search Engine Demand Index	15.26 (26.88)
Search Engine Supply Index	2.00 (0.95)

This Compound (18.92)

All Compounds (24.57)

Study Types

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	7 (38.89%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	11 (61.11%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
carbostyril Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.	3.14	1	monohydroxyquinoline; quinolone	bacterial xenobiotic metabolite
cytidine monophosphate Cytidine Monophosphate: Cytidine (dihydrogen phosphate). A cytosine nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.. cytidine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having cytosine as the nucleobase.	2.06	1	cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-monophosphate	Escherichia coli metabolite; human metabolite; mouse metabolite
cytidine [no description available]	9.06	4	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.	2.05	1	cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-triphosphate	Escherichia coli metabolite; mouse metabolite
thiazoles [no description available]	3.15	1	1,3-thiazoles; mancude organic heteromonocyclic parent; monocyclic heteroarene
deoxycytidine [no description available]	2.02	1	pyrimidine 2'-deoxyribonucleoside	Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite
ribavirin Rebetron: Rebetron is tradename	4.9	4	1-ribosyltriazole; aromatic amide; monocarboxylic acid amide; primary carboxamide	anticoronaviral agent; antiinfective agent; antimetabolite; antiviral agent; EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
nitazoxanide nitazoxanide: a 5-nitrothiazolyl derivative used for a broad range of intestinal parasitic infections including CRYPTOSPORIDIUM and GIARDIA; it is a redox-active nitrothiazolyl-salicylamide prodrug	3.15	1	benzamides; carboxylic ester
proline Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. proline : An alpha-amino acid that is pyrrolidine bearing a carboxy substituent at position 2.	4.05	2	amino acid zwitterion; glutamine family amino acid; L-alpha-amino acid; proline; proteinogenic amino acid	algal metabolite; compatible osmolytes; Escherichia coli metabolite; micronutrient; mouse metabolite; nutraceutical; Saccharomyces cerevisiae metabolite
taribavirin [no description available]	3.53	2	nucleobase-containing molecular entity
4'-azidocytidine 4'-azidocytidine: antiviral; structure in first source	3.83	3	N-glycosyl compound
2'-c-methyladenosine 2'-C-methyladenosine: antiviral	2.03	1
2'-c-methylcytidine 2'-C-methylcytidine: structure in first source	7.96	4
telaprevir [no description available]	5.49	6	cyclopentapyrrole; cyclopropanes; oligopeptide; pyrazines	antiviral drug; hepatitis C protease inhibitor; peptidomimetic
mk 0608 7-deaza-2'-C-methyladenosine: an antiviral agent	2.03	1
jtk-303 [no description available]	3.14	1	aromatic ether; monochlorobenzenes; organofluorine compound; quinolinemonocarboxylic acid; quinolone	HIV-1 integrase inhibitor
psi 6130 2'-deoxy-2'-fluoro-2'-C-methylcytidine: PSI-6130 is the (beta-D)-isomer; has antiviral activity against hepatitis C virus; structure in first source	2.04	1
hcv 796 HCV 796: inhibits HCV RdRp; structure in first source	2.04	1
balapiravir balapiravir: a prodrug of R1479; structure in first source	3.83	3
losartan potassium Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.	3.13	1
rg 7128 2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine: inhibits HCV polymerase; structure in first source	2.05	1
raltegravir potassium Raltegravir Potassium: A pyrrolidinone derivative and HIV INTEGRASE INHIBITOR that is used in combination with other ANTI-HIV AGENTS for the treatment of HIV INFECTION.	3.14	1

Condition	Indicated	Relationship Strength	Studies
Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted [description not available]	0	4.81	7
Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.	0	9.81	7
Chronic Hepatitis C [description not available]	0	5.43	6
HIV Coinfection [description not available]	0	3.83	2
Drug Abuse, Intravenous [description not available]	0	2.96	1
HIV Infections Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).	0	3.83	2
Hepatitis C, Chronic INFLAMMATION of the LIVER in humans that is caused by HEPATITIS C VIRUS lasting six months or more. Chronic hepatitis C can lead to LIVER CIRRHOSIS.	1	7.43	6
Cirrhosis, Liver [description not available]	0	2.94	1
Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.	0	2.94	1

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