SOFOSBUVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H29FN3O9P
Molecular Weight	529.4525
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)OC(=O)[C@H](C)N[P@](=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-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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf
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

Originator

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis C 42 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf	Primary		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
922.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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

Value	Dose	Co-administered	Analyte	Population
872.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ribavirin	Ribavirin	SOFOSBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
861 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.35 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ribavirin	Ribavirin	SOFOSBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.38 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30185395/	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
63% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/204671s002lbl.pdf	400 mg 1 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ribavirin	Ribavirin	SOFOSBUVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/30900816	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: https://pubmed.ncbi.nlm.nih.gov/30900816	Other AEs: Creatine phosphokinase increased, Rash... Other AEs: Creatine phosphokinase increased (1 patient) Rash (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/30900816

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/30900816	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: https://pubmed.ncbi.nlm.nih.gov/30900816
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: https://pubmed.ncbi.nlm.nih.gov/30900816	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: https://pubmed.ncbi.nlm.nih.gov/30900816

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85083	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85083
ZINC	ZINC000100074252	http://zinc15.docking.org/substances/ZINC000100074252

PubMed

Title	Date	PubMed
Changing the face of hepatitis C management - the design and development of sofosbuvir.	2015	25987834
Cost-effectiveness of sofosbuvir-based treatments for chronic hepatitis C in the US.	2015 Aug 5	26239358
Hepatitis C virus: Virology, diagnosis and treatment.	2015 Jun 8	26052383
Finding Truth in a World Full of Spin: Myth-Busting in the Case of Sovaldi.	2015 May 1	25850880
Interferon-free therapy for hepatitis C: The hurdles amid a golden era.	2015 Sep	25937625

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage of SOVALDI is one 400 mg tablet, taken orally, once daily with or without food.

Route of Administration: Oral

In Vitro Use Guide

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

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 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 [WHO-DD]

Common 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