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Details

Stereochemistry ABSOLUTE
Molecular Formula C10H14FN3O4
Molecular Weight 259.2343
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PSI-6130

SMILES

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

InChI

InChIKey=NYPIRLYMDJMKGW-VPCXQMTMSA-N
InChI=1S/C10H14FN3O4/c1-10(11)7(16)5(4-15)18-8(10)14-3-2-6(12)13-9(14)17/h2-3,5,7-8,15-16H,4H2,1H3,(H2,12,13,17)/t5-,7-,8-,10-/m1/s1

HIDE SMILES / InChI

Description

Mericitabine is a specific inhibitor of hepatitis C virus (HCV) replication that target NS5B polymerase. Mericitabine, a prodrug, is hydrolyzed in vivo to produce PSI-6130. It had been studied in phase II clinical trials for the treatment of chronic hepatitis C. However, while it showed a good safety profile in clinical trials, it was not sufficiently effective to be used as a standalone agent.

Originator

Pharmasset
5

Approval Year

Unknown
149,124

Targets

Primary TargetPharmacologyConditionPotency
Hepatitis C virus NS5B RNA-dependent RNA polymerase
14
Inhibitor
8,504
 0.61 µM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Hepatitis C
42
 Primary
Phase II
1,147
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
0.854 μg/mL
2000 mg single, oral
 RO5012433 plasma
Homo sapiens
0.361 μg/mL
500 mg single, oral
 RO5012433 plasma
Homo sapiens
0.557 μg/mL
1000 mg single, oral
 RO5012433 plasma
Homo sapiens
10.2 μg/mL
2000 mg single, oral
 RO4995855 plasma
Homo sapiens
4.23 μg/mL
500 mg single, oral
 RO4995855 plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
20.5 μg × h/mL
2000 mg single, oral
 RO5012433 plasma
Homo sapiens
6.35 μg × h/mL
500 mg single, oral
 RO5012433 plasma
Homo sapiens
11.2 μg × h/mL
1000 mg single, oral
 RO5012433 plasma
Homo sapiens
113 μg × h/mL
2000 mg single, oral
 RO4995855 plasma
Homo sapiens
28.8 μg × h/mL
500 mg single, oral
 RO4995855 plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
21.8 h
2000 mg single, oral
 RO5012433 plasma
Homo sapiens
19 h
500 mg single, oral
 RO5012433 plasma
Homo sapiens
22.7 h
1000 mg single, oral
 RO5012433 plasma
Homo sapiens
5.54 h
2000 mg single, oral
 RO4995855 plasma
Homo sapiens
4.96 h
500 mg single, oral
 RO4995855 plasma
Homo sapiens

PubMed

Patents

20070197463
2
US20130172239
2
WO2013178571A1
2

Sample Use Guides

In Vivo Use Guide
1500 mg doses twice daily for 2 weeks
Route of Administration: Oral
In Vitro Use Guide
A stable HCV 1b replicon cell (Gt 1b Con1) line was treated with the NS5B nucleoside inhibitor R7128 (prodrug PSI-6130). Inhibition of HCV replicon-encoded Renilla luciferase reporter activity after 3 days of incubation was calculated - EC50 = 0.61 uM.
PRODRUG (METABOLITE ACTIVE)
Structure of MERICITABINE
SUBSTANCE RECORD
Structure of PSI-6130
NIH
NCATS
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