VALOPICITABINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H24N4O6
Molecular Weight	356.3743
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)[C@H](N)C(=O)O[C@@H]1[C@@H](CO)O[C@@H](N2C=CC(N)=NC2=O)[C@]1(C)O

InChI

InChIKey=TVRCRTJYMVTEFS-ICGCPXGVSA-N

InChI=1S/C15H24N4O6/c1-7(2)10(17)12(21)25-11-8(6-20)24-13(15(11,3)23)19-5-4-9(16)18-14(19)22/h4-5,7-8,10-11,13,20,23H,6,17H2,1-3H3,(H2,16,18,22)/t8-,10+,11-,13-,15-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C15H24N4O6
Molecular Weight	356.3743
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17064080 | http://www.jbc.org/content/283/4/2167.full#T4 | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346640/ | https://www.ncbi.nlm.nih.gov/pubmed/23986582 | https://www.ncbi.nlm.nih.gov/pubmed/27252124 | https://www.ncbi.nlm.nih.gov/pubmed/21709100https://www.ncbi.nlm.nih.gov/pubmed/17328231 | https://www.ncbi.nlm.nih.gov/pubmed/18479202 | https://www.thepharmaletter.com/article/fda-puts-clinical-hold-on-valopicitabine-over-risk-benefit-profile-idenix-plunges-34

Valopicitabine is a nucleoside analog and the orally bioavailable prodrug of NM107 that competitively inhibits HCV NS5B polymerase, causing chain termination. Valopicitabine had been in phase II clinical trial for once-daily oral treatment of Hepatitis C virus infection. However, because of the overall risk/benefit profile of subjects undergoing clinical trials, further development of the drug has been temporarily placed on hold by the Swiss drug major Novartis and USA-based Idenix Pharmaceuticals company and the FDA.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14 Target ID: CHEMBL5375 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18479202	Inhibitor 8297	0.5 µM [IC50]
Hepatitis C virus NS5B RNA-dependent RNA polymerase 14 Target ID: CHEMBL5375 Sources: http://www.jbc.org/content/283/4/2167.full#T4	Inhibitor 8297	1.05 µM [IC50]
human norovirus replication 3 Target ID: human norovirus replication Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807313/	Inhibitor 8297	18.0 µM [EC50]
Picornaviridae 3 Target ID: CHEMBL613008 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17055073	Inhibitor 8297	6.4 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Chronic hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18479202 https://clinicaltrials.gov/ct2/show/NCT00120835 https://clinicaltrials.gov/ct2/show/NCT00118768	Primary	Phase II 1132	Unknown Approved Use Unknown
Gastroenteritis 10 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27252124	Primary	Basic research	Unknown Approved Use Unknown
Foot-and-mouth disease virus 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17055073	Primary	Basic research	Unknown Approved Use Unknown
Hepatitis C 42 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16787301 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2346640/	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Nm 283, an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine.	2005	16248033
Synthesis and pharmacokinetics of valopicitabine (NM283), an efficient prodrug of the potent anti-HCV agent 2'-C-methylcytidine.	2006 Nov 2	17064080
Ribavirin antagonizes the in vitro anti-hepatitis C virus activity of 2'-C-methylcytidine, the active component of valopicitabine.	2006 Oct	17005827
Pyrophosphorolytic excision of nonobligate chain terminators by hepatitis C virus NS5B polymerase.	2007 Aug	17502402
2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virus.	2007 Mar	17055073
The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors.	2008 May	18285474
The hepatitis C virus (HCV) NS4B RNA binding inhibitor clemizole is highly synergistic with HCV protease inhibitors.	2010 Jul 1	20486856
Comparative study of the genetic barriers and pathways towards resistance of selective inhibitors of hepatitis C virus replication.	2011 Sep	21709100
The viral polymerase inhibitor 2'-C-methylcytidine inhibits Norwalk virus replication and protects against norovirus-induced diarrhea and mortality in a mouse model.	2013 Nov	23986582
Biochemical Evaluation of the Inhibition Properties of Favipiravir and 2'-C-Methyl-Cytidine Triphosphates against Human and Mouse Norovirus RNA Polymerases.	2015 Dec	26392512
Treatment with a Nucleoside Polymerase Inhibitor Reduces Shedding of Murine Norovirus in Stool to Undetectable Levels without Emergence of Drug-Resistant Variants.	2015 Dec 28	26711754
Post-exposure antiviral treatment of norovirus infections effectively protects against diarrhea and reduces virus shedding in the stool in a mortality mouse model.	2016 Aug	27252124

Patents

Sample Use Guides

In Vivo Use Guide

Treatment with 2CMC (2'-C-methylcytidine ) was initiated 1 h before human norovirus infection with a dose of 100 mg/kg/day divided into two daily treatments (2 × 50 mg/kg) for 7 consecutive days by the subcutaneous route (n = 15).

Route of Administration: Other

In Vitro Use Guide

The 50% and 90% effective concentrations (EC50 and EC90) for inhibition of the foot-and-mouth disease virus (FMDV) - induced cytopathic effect (CPE) formation were 6.4+/-3.8 and 10.8+/-5.4 uM. Comparable EC50 values for inhibition of viral RNA synthesis were observed. Treatment of FMDV-infected BHK-21 cells with 77 uM 2'-C-MetCyt resulted in a (1.6-3.2)x10(3)-fold reduction of infectious virus yield.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:29:13 UTC 2023` Edited by `admin` on `Fri Dec 15 15:29:13 UTC 2023`
Record UNII	I2T0B5G94M
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VALOPICITABINE

Official Name

English

NM-283

Code

English

NM283

Code

English

valopicitabine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1557