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Details

Stereochemistry EPIMERIC
Molecular Formula C22H29FN3O9P
Molecular Weight 529.4525
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PSI-7851

SMILES

CC(C)OC(=O)[C@H](C)NP(=O)(OC[C@H]1O[C@@H](N2C=CC(=O)NC2=O)[C@](C)(F)[C@@H]1O)OC3=CC=CC=C3

InChI

InChIKey=TTZHDVOVKQGIBA-IAAJYNJHSA-N
InChI=1S/C22H29FN3O9P/c1-13(2)33-19(29)14(3)25-36(31,35-15-8-6-5-7-9-15)32-12-16-18(28)22(4,23)20(34-16)26-11-10-17(27)24-21(26)30/h5-11,13-14,16,18,20,28H,12H2,1-4H3,(H,25,31)(H,24,27,30)/t14-,16+,18+,20+,22+,36?/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H29FN3O9P
Molecular Weight 529.4525
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20801890 | https://www.ncbi.nlm.nih.gov/pubmed/20516278

GS-9851 (formerly PSI 7851) is an orally available, second generation uridine nucleoside analog polymerase inhibitor of hepatitis C treatment. GS-9851 is a nucleotide prodrug of the nucleoside analog GS-331007 (formerly PSI-6206). GS-9851 potently inhibits HCV NS5B polymerase and has demonstrated pan-genotypic activity in vitro. Preclinical studies of GS-9851 demonstrated a favorable profile in terms of antiviral potency, distribution, and metabolism. GS-9851 is first hydrolyzed to the intermediate GS-566500 (formerly PSI-352707), which is then metabolized to either the inactive metabolite, GS-331007, or the monophosphate GS-606965 (formerly PSI-7411). Inside the hepatocyte, GS-606965 is further phosphorylated by a series of enzymatic steps to an active triphosphate metabolite, GS-461203 (formerly PSI-7409), that selectively inhibits recombinant NS5B. A first-time-in-human study demonstrated that GS-9851 (25 to 800 mg) is generally safe and well tolerated in patients chronically infected with HCV. GS-9851 has a pharmacokinetic profile consistent with once-daily dosing. Administration of GS-9851 led to significant reductions in plasma HCV RNA levels without the evolution of known resistance mutations.

Originator

Sources: Abstracts of Papers, 238th ACS National Meeting, Washington, DC, United States, August 16-20, 2009 (2009), COMP-023.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
218.9 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
336.6 ng/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
340.4 ng/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
117.7 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
29.1 ng/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
13.3 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
46.2 ng/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
32.8 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
81 ng/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
77.1 ng/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
81.69 ng/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
21.5 ng/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1719.9 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2947.7 ng × h/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3554.4 ng × h/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
951.5 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
105.7 ng × h/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
21.3 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
215 ng × h/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
91.5 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
113.2 ng × h/mL
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
159.7 ng × h/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
191.5 ng × h/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
35.1 ng × h/mL
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.3 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.2 h
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
17.9 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6 h
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
RO-2433 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.3 h
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.7 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.3 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
GS-566500 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1 h
100 mg 1 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1.3 h
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1 h
50 mg 1 times / day steady-state, oral
dose: 50 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PSI-7851 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: hepatitis C infection
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Other AEs: Nausea, Absolute neutrophil count decreased...
Other AEs:
Nausea (1 pt)
Absolute neutrophil count decreased (1 pt)
Sources:
800 mg single, oral (total daily dose)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Other AEs: Dizziness, Abdominal pain...
Other AEs:
Dizziness (moderate, 13%)
Abdominal pain (13%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Absolute neutrophil count decreased 1 pt
400 mg 1 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: hepatitis C infection
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Nausea 1 pt
400 mg 1 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy
n = 8
Health Status: unhealthy
Condition: hepatitis C infection
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Abdominal pain 13%
800 mg single, oral (total daily dose)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Dizziness moderate, 13%
800 mg single, oral (total daily dose)
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
healthy
n = 8
Health Status: healthy
Sex: M+F
Food Status: FASTED
Population Size: 8
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics, safety, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor for hepatitis C virus, following single ascending doses in healthy subjects.
2013 Mar
Pharmacokinetics, pharmacodynamics, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor, following multiple ascending doses in patients with chronic hepatitis C infection.
2013 Mar
Patents

Patents

Sample Use Guides

Patients received active doses up to 400 mg of GS-9851 once daily for 3 days
Route of Administration: Oral
Huh7, HepG2, BxPC3, and CEM cells were treated with PSI-7851 (GS-9851, serially diluted from 100 mkM in medium containing dimethyl sulfoxide [DMSO]), Gemcitabine (1mkM), or DMSO control for 8 days. A cell viability assay was performed using the CellTiter 96 Aqueous One Solution cell proliferation assay kit as recommended by the manufacturer (Promega). The absorbance at 490 nm was read with a Victor3 plate reader (Perkin Elmer) using the medium-only control wells as blanks.
Substance Class Chemical
Created
by admin
on Sat Dec 16 09:09:28 UTC 2023
Edited
by admin
on Sat Dec 16 09:09:28 UTC 2023
Record UNII
3S5S1851OV
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PSI-7851
Common Name English
GS-9851
Code English
PSI 7851
Code English
N-((2'R)-2'-DEOXY-2'-FLUORO-2'-METHYL-P-PHENYL-5'-URIDYLYL)-L-ALANINE 1-METHYLETHYL ESTER
Systematic Name English
L-ALANINE, N-((2'R)-2'-DEOXY-2'-FLUORO-2'-METHYL-P-PHENYL-5'-URIDYLYL)-, 1-METHYLETHYL ESTER
Systematic Name English
Code System Code Type Description
CAS
1221574-17-9
Created by admin on Sat Dec 16 09:09:28 UTC 2023 , Edited by admin on Sat Dec 16 09:09:28 UTC 2023
SUPERSEDED
CAS
1064684-44-1
Created by admin on Sat Dec 16 09:09:28 UTC 2023 , Edited by admin on Sat Dec 16 09:09:28 UTC 2023
PRIMARY
FDA UNII
3S5S1851OV
Created by admin on Sat Dec 16 09:09:28 UTC 2023 , Edited by admin on Sat Dec 16 09:09:28 UTC 2023
PRIMARY
PUBCHEM
45375806
Created by admin on Sat Dec 16 09:09:28 UTC 2023 , Edited by admin on Sat Dec 16 09:09:28 UTC 2023
PRIMARY
Related Record Type Details
DIASTEREOISOMER -> EPIMER