U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C22H29FN3O9P
Molecular Weight 529.4534
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SOFOSBUVIR

SMILES

CC(C)OC(=O)[C@]([H])(C)N[P@](=O)(OC[C@]1([H])[C@]([H])([C@](C)([C@]([H])(n2ccc(nc2=O)O)O1)F)O)Oc3ccccc3

InChI

InChIKey=TTZHDVOVKQGIBA-IQWMDFIBSA-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

Description
Curator's Comment:: description was created based on several sources, including https://www.quora.com/How-was-Sovaldi-the-drug-now-being-marketed-by-Gilead-first-discovered-by-Pharmasset

Sofosbuvir is a nucleotide analog inhibitor of hepatitis C virus NS5B polymerase - the key enzyme mediating HCV RNA replication. Sofosbuvir is a prodrug and after ingestion it is rapidly converted to GS-331007, the predominant circulating drug that accounts for greater than 90% of the systemically active drug. The compound GS-331007 is efficiently taken up by hepatocytes, whereby cellular kinases convert GS-331007 to its pharmacologically active uridine analog 5’-triphosphate form (GS-461203). This triphosphate compound mimics the natural cellular uridine nucleotide and is incorporated by the HCV RNA polymerase into the elongating RNA primer strand, resulting in chain termination. The active form GS-461203 targets the NS5B catalytic site and acts as a non-obligate chain terminator. The active compound (GS-461203) does not inhibit host DNA polymerases, RNA polymerases, or mitochondrial RNA polymerase. Sofosbuvir (alone or in in combination with other medications) is used to treat Hepatitis C.

CNS Activity

Curator's Comment:: Drug derived radioactivity was detected in CNS tissues and testes at the 1 h time point in both albino and pigmented rats but was below the limitation of quantitation.The penetration of the blood-brain and blood-testes barriers appeared limited as the concentrations of drug derived radioactivity in these tissues were among the lowest along with bone, eye lens, and white adipose tissue. Human data not available.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
SOVALDI

Approved Use

SOVALDI is indicated for the treatment of genotype 1, 2, 3 or 4 chronic hepatitis C virus (HCV) infection as a component of a combination antiviral treatment regimen.

Launch Date

1.38628799E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
922.3 ng/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1001.7 ng/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
872.2 ng × h/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
969 ng × h/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ribavirin
SOFOSBUVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
861 ng × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.35 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.4 h
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ribavirin
SOFOSBUVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.38 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SOFOSBUVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
63%
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ribavirin
SOFOSBUVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
healthy, 35.56 years (range: 18-45 years)
n = 12
Health Status: healthy
Age Group: 35.56 years (range: 18-45 years)
Sex: M+F
Population Size: 12
Sources:
Other AEs: Creatine phosphokinase increased, Rash...
Other AEs:
Creatine phosphokinase increased (1 patient)
Rash (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Creatine phosphokinase increased 1 patient
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
healthy, 35.56 years (range: 18-45 years)
n = 12
Health Status: healthy
Age Group: 35.56 years (range: 18-45 years)
Sex: M+F
Population Size: 12
Sources:
Rash 1 patient
400 mg 1 times / day multiple, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
healthy, 35.56 years (range: 18-45 years)
n = 12
Health Status: healthy
Age Group: 35.56 years (range: 18-45 years)
Sex: M+F
Population Size: 12
Sources:
PubMed

PubMed

TitleDatePubMed
Highly efficient infectious cell culture of three hepatitis C virus genotype 2b strains and sensitivity to lead protease, nonstructural protein 5A, and polymerase inhibitors.
2014 Feb
The combination of alisporivir plus an NS5A inhibitor provides additive to synergistic anti-hepatitis C virus activity without detectable cross-resistance.
2014 Jun
Intracellular effects of the Hepatitis C virus nucleoside polymerase inhibitor RO5855 (Mericitabine Parent) and Ribavirin in combination.
2014 May
Changing the face of hepatitis C management - the design and development of sofosbuvir.
2015
Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.
2015 Aug 5
Hepatitis C virus: Virology, diagnosis and treatment.
2015 Jun 8
Finding Truth in a World Full of Spin: Myth-Busting in the Case of Sovaldi.
2015 May 1
Interferon-free therapy for hepatitis C: The hurdles amid a golden era.
2015 Sep
Patents

Sample Use Guides

The recommended dosage of SOVALDI is one 400 mg tablet, taken orally, once daily with or without food.
Route of Administration: Oral
In HCV replicon assays, the EC50 values of sofosbuvir against full-length replicons from genotype 1a, 1b, 2a, 3a and 4a, and chimeric 1b replicons encoding NS5B from genotype 2b, 5a or 6a ranged from 0.014 to 0.11 micromolar. The median EC50 value of sofosbuvir against chimeric replicons encoding NS5B sequences from clinical isolates was 0.062 micromolar for genotype 1a (range 0.029–0.128 micromolar; N=67), 0.102 micromolar for genotype 1b (range 0.045–0.170 micromolar; N=29), 0.029 micromolar for genotype 2 (range 0.014–0.081 micromolar; N=15) and 0.081 micromolar for genotype 3a (range 0.024–0.181 micromolar; N=106). In infectious virus assays, the EC50 values of sofosbuvir against genotype 1a and 2a were 0.03 and 0.02 micromolar, respectively. The presence of 40% human serum had no effect on the anti-HCV activity of sofosbuvir. Evaluation of sofosbuvir in combination with interferon alpha or ribavirin showed no antagonistic effect in reducing HCV RNA levels in replicon cells.
Name Type Language
SOFOSBUVIR
DASH   INN   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
SOFOSBUVIR [INN]
Common Name English
SOFOSBUVIR [VANDF]
Common Name English
HARVONI COMPONENT SOFOSBUVIR
Brand Name English
EPCLUSA COMPONENT SOFOSBUVIR
Brand Name English
GS-7977
Code English
SOFOSBUVIR [WHO-DD]
Common Name English
SOFOSBUVIR COMPONENT OF VOSEVI
Brand Name English
L-ALANINE, N-((P(S),2'R)-2'-DEOXY-2'-FLUORO-2'-METHYL-P-PHENYL-5'-URIDYLYL)-, 1-METHYLETHYL ESTER
Common Name English
SOFOSBUVIR [USAN]
Common Name English
SOF
Common Name English
SOVALDI
Brand Name English
(S)-ISOPROPYL 2-((S)-(((2R,3R,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-4-FLUORO-3-HYDROXY-4-METHYLTETRAHYDROFURAN-2-YL)METHOXY)-(PHENOXY)PHOSPHORYLAMINO)PROPANOATE
Systematic Name English
SOFOSBUVIR COMPONENT OF HARVONI
Brand Name English
SOFOSBUVIR COMPONENT OF EPCLUSA
Brand Name English
SOFOSBUVIR [MI]
Common Name English
PSI-7977
Code English
SOFOSBUVIR [ORANGE BOOK]
Common Name English
GS7977
Code English
VOSEVI COMPONENT SOFOSBUVIR
Brand Name English
SOFOSBUVIR [JAN]
Common Name English
Classification Tree Code System Code
WHO-ATC J05AP55
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
NCI_THESAURUS C281
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
WHO-ATC J05AX65
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
WHO-ATC J05AX15
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
FDA ORPHAN DRUG 535916
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
WHO-ATC J05AP08
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
EMA ASSESSMENT REPORTS SOVALDI (AUTHORIZED: HEPATITIS C, CHRONIC)
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
NDF-RT N0000191493
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
NCI_THESAURUS C25995
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
FDA ORPHAN DRUG 541716
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
WHO-ATC J05AP51
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
EMA ASSESSMENT REPORTS HARVONI (AUTHORIZED: HEPATITIS C, CHRONIC)
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
WHO-ATC J05AP56
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
FDA ORPHAN DRUG 554816
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
Code System Code Type Description
IUPHAR
7368
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
HSDB
8226
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
MERCK INDEX
M11680
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
WIKIPEDIA
SOFOSBUVIR
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
NCI_THESAURUS
C101263
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
INN
9665
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
DRUG BANK
DB08934
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
CAS
1190307-88-0
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
NDF-RT
N0000191258
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY RNA Replicase Inhibitors [MoA]
RXCUI
1484911
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY RxNorm
FDA UNII
WJ6CA3ZU8B
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
ChEMBL
CHEMBL1259059
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
DRUG CENTRAL
4811
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
PUBCHEM
45375808
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
LACTMED
Sofosbuvir
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY
EVMPD
SUB121170
Created by admin on Sat Jun 26 02:52:49 UTC 2021 , Edited by admin on Sat Jun 26 02:52:49 UTC 2021
PRIMARY