Sofosbuvir

Identification

Summary

Sofosbuvir is a direct-acting antiviral agent used to treat specific hepatitis C virus (HCV) infections in combination with other antiviral agents.

Brand Names

Epclusa, Harvoni, Sovaldi, Vosevi

Generic Name

Sofosbuvir

DrugBank Accession Number

DB08934

Background

Sofosbuvir (tradename Sovaldi) is a direct acting antiviral medication used as part of combination therapy to treat chronic Hepatitis C, an infectious liver disease caused by infection with Hepatitis C Virus (HCV). HCV is a single-stranded RNA virus that is categorized into nine distinct genotypes, with genotype 1 being the most common in the United States, and affecting 72% of all chronic HCV patients ¹⁴. Treatment options for chronic Hepatitis C have advanced significantly since 2011, with the development of Direct Acting Antivirals (DAAs) such as sofosbuvir. As a prodrug nucleotide analog, Sofosbuvir is metabolized into its active form as the antiviral agent 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (also known as GS-461203), which acts as a defective substrate for NS5B (non-structural protein 5B) ^Synthesis. NS5B, an RNA-dependent RNA polymerase, is essential for the transcription of Hepatitis C viral RNA and for its high replicative rate and genetic diversity ⁴. Sofosbuvir and other direct acting antivirals are therefore very potent options for the treatment of Hepatitis C, as they exhibit a high barrier to the development of resistance ⁵. This is an important advantage relative to HCV drugs that target other viral enzymes such as the protease, for which rapid development of resistance has proven to be an important cause of therapeutic failure.

In a joint recommendation published in 2016, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend Sofosbuvir as first line therapy in combination with other antivirals for all six genotypes of Hepatitis C ¹⁴. Depending on the genotype, sofosbuvir is often used in combination with other antivirals such as Ledipasvir, Velpatasvir, Daclatasvir, Simeprevir, Elbasvir, Grazoprevir, Ribavirin, Peginterferon alfa-2a, or Peginterferon alfa-2b with the intent to cure, or achieve a sustained virologic response (SVR), after 12 weeks of daily therapy. SVR and eradication of HCV infection is associated with significant long-term health benefits including reduced liver-related damage, improved quality of life, reduced incidence of Hepatocellular Carcinoma, and reduced all-cause mortality ⁶. Treatment with direct acting antivirals such as sofosbuvir is associated with very minimal side effects, with the most common being headache and fatigue ^Label. Lack of significant side effects and short duration of therapy is a considerable advantage over older interferon- and ribavirin-based regimens, which were limited by infusion site reactions, reduced blood count, and neuropsychiatric effects ¹¹.

Since 2014, sofosbuvir has been available as a fixed dose combination product with Ledipasvir (tradename Harvoni) used for the treatment of chronic Hepatitis C. Approved in October 2014 by the FDA, Harvoni is indicated for the treatment of HCV genotypes 1, 4, 5, and 6 with or without Ribavirin depending on the level of liver damage or cirrhosis ^Label. When combined together, ledipasvir and sofosbuvir as the combination product Harvoni has been shown to achieve a SVR between 93 and 99% after 12 weeks of treatment ³. Its use has also proven successful in the treatment of HCV in patients co-infected with HIV ⁷.

Sofosbuvir is also available as a fixed dose combination product with Velpatasvir as the commercially available product Epclusa. First approved in June 2016, Epclusa is the first combination HCV product indicated for the treatment of all genotypes of Hepatitis C with or without cirrhosis. Epclusa is also currently the most potent HCV antiviral medication on the market with a sustained virologic response (SVR) after 12 weeks of therapy of 93-99% depending on genotype and level of cirrhosis ¹⁴. Both Canadian and American guidelines list Epclusa as a first line recommendation for all genotypes of HCV ^14,6.

Notably, sofosbuvir has come under intense scrutiny since its release to market in 2013. With the price per pill set at $1000, a 12-week treatment can cost upwards of $84,000 per patient ¹².

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 529.458
Monoisotopic: 529.162544687
Chemical Formula: C₂₂H₂₉FN₃O₉P

Synonyms

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
Sofosbuvir

External IDs

GI 7977
GI-7977
GI7977
GS 331007
GS 461203
GS-331007
GS-461203
GS-7977
GS331007
GS461203
GS7977
PSI 7977
PSI-7977
PSI7977

Pharmacology

Indication

Sofosbuvir is used in combination therapy with other antiviral medications to treat chronic hepatitis C virus (HCV) infected patients with HCV genoptypes 1-6, and to treat HCV and HIV co-infected patients. Depending on the level of cirrhosis or decompensation, combination therapy can also include either ribavirin alone or ribavirin and peg-interferon alfa.

When used in combination with Ledipasvir, sofosbuvir has the following indications: treatment of genotypes 1, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis; in combination with Ribavirin for genotype 1 infection with decompensated cirrhosis; or in combination with Ribavirin for the treatment of genotype 1 or 4 infection who are liver transplant recipients without cirrhosis or with compensated cirrhosis.

When used in combination with Velpatasvir as the combination product Epclusa, sofosbuvir is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis, or in combination with Ribavirin if associated with decompensated cirrhosis.

Resistance: Reduced susceptibility to sofosbuvir has been associated with the NS5B substitution mutation S282T ¹⁰.

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Sofosbuvir acts against HCV and is categorized as a direct-acting antiviral agent (DAA).

At a dose 3 times the recommended dose, sofosbuvir does not prolong QTc to any clinically relevant extent ^Label.

Mechanism of action

Sofosbuvir is nucleotide analog inhibitor, which specifically inhibits HCV NS5B (non-structural protein 5B) RNA-dependent RNA polymerase. Following intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), sofosbuvir incorporates into HCV RNA by the NS5B polymerase and acts as a chain terminator ^Synthesis,2. More specifically, Sofosbuvir prevents HCV viral replication by binding to the two Mg2+ ions present in HCV NS5B polymerase's GDD active site motif and preventing further replication of HCV genetic material ^13,Label.

Target	Actions	Organism
ARNA-dependent RNA-polymerase	inhibitor	Hepatitis C Virus

Absorption

When given orally, sofosbuvir reaches its maximum plasma concentration in about 0.5 to 2 hours with a maximal concentration (Cmax) of 567 ng/mL ^Label.

Volume of distribution

The volume of distribution for sofosbuvir has yet to be determined ^Label.

Protein binding

Sofosbuvir is approximately 61-65% bound to human plasma proteins ^Label.

Metabolism

In vitro studies in human liver microsomes showed that sofosbuvir was an efficient substrate for Cathepsin A (Cat A) and carboxyl esterase 1 (CES1). Sofosbuvir was cleaved by CatA and CES1 and subsequent activation steps included amino acid removal by histidine triad nucleotide-binding protein 1 (HINT1) and phosphorylation by uridine monophosphate-cytidine monophosphate (UMP-CMP) kinase and nucleoside diphosphate (NDP) kinase. In vitro data indicated that Cat A preferentially hydrolysed sofosbuvir (the S-diastereomer) while CES1 did not exhibit stereoselectivity ^8,9.

Hover over products below to view reaction partners

Sofosbuvir
- GS-56650
  - GS-606965
    - GS-461203

Route of elimination

Sofosbuvir is eliminated by three routes: urine ( 80%), feces (14%), and respiration (2.5%); however, elimination through the kidneys is the major route ^Label.

Half-life

Sofosbuvir has a terminal half life of 0.4 hours ^Label.

Clearance

The clearance of sofosbuvir has yet to be determined ^Label.

Adverse Effects

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Toxicity

Sofosbuvir, as a single agent, has very mild toxicity. The most common adverse reactions are headache and fatigue. The FDA Label currently warns of a risk of symptomatic bradycardia when Epclusa is used in combination with amiodarone ^Label.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abacavir	Abacavir may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Abemaciclib	Abemaciclib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Abrocitinib	The serum concentration of Sofosbuvir can be increased when it is combined with Abrocitinib.
Aceclofenac	Aceclofenac may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Acetaminophen	Acetaminophen may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Acetazolamide	Acetazolamide may increase the excretion rate of Sofosbuvir which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acid	Acetylsalicylic acid may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Aclidinium	Aclidinium may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Acrivastine	Sofosbuvir may decrease the excretion rate of Acrivastine which could result in a higher serum level.

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Food Interactions

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Products

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International/Other Brands

Hepcinat (Natco Pharma Ltd.) / Hepcvir (Cipla Limited) / Resof (Hetero Drugs Ltd ) / SoviHep (Zydus Cadila)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Sovaldi	Pellet	150 mg	Oral	Gilead Sciences Ireland Uc	2020-12-22	Not applicable
Sovaldi	Tablet	400 mg	Oral	Gilead Sciences	2014-01-06	Not applicable
Sovaldi	Tablet, film coated	400 mg	Oral	Gilead Sciences Ireland Uc	2016-09-08	Not applicable
Sovaldi	Tablet, film coated	200 mg/1	Oral	Gilead Sciences, Inc.	2019-08-28	Not applicable
Sovaldi	Tablet, film coated	200 mg	Oral	Gilead Sciences Ireland Uc	2020-12-22	Not applicable
Sovaldi	Pellet	200 mg/1	Oral	Gilead Sciences, Inc.	2019-08-28	Not applicable
Sovaldi	Tablet	200 mg	Oral	Gilead Sciences Ireland Uc	2020-12-22	Not applicable
Sovaldi	Tablet, film coated	400 mg/1	Oral	Gilead Sciences, Inc.	2013-12-06	Not applicable
Sovaldi	Tablet, film coated	400 mg	Oral	Gilead Sciences Ireland Uc	2016-09-08	Not applicable
Sovaldi	Pellet	150 mg/1	Oral	Gilead Sciences, Inc.	2019-08-28	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Epclusa	Sofosbuvir (200 mg/1) + Velpatasvir (50 mg/1)	Pellet	Oral	Gilead Sciences, Inc.	2021-06-10	Not applicable
Epclusa	Sofosbuvir (150 mg) + Velpatasvir (37.5 mg)	Pellet	Oral	Gilead Sciences Ireland Uc	2022-06-08	Not applicable
Epclusa	Sofosbuvir (200 mg/1) + Velpatasvir (50 mg/1)	Tablet, film coated	Oral	Gilead Sciences, Inc.	2020-03-19	Not applicable
Epclusa	Sofosbuvir (200 mg) + Velpatasvir (50 mg)	Tablet, film coated	Oral	Gilead Sciences Ireland Uc	2020-12-23	Not applicable
Epclusa	Sofosbuvir (400 mg) + Velpatasvir (100 mg)	Tablet	Oral	Gilead Sciences	2016-08-02	Not applicable
Epclusa	Sofosbuvir (400 mg/1) + Velpatasvir (100 mg/1)	Tablet, film coated	Oral	Gilead Sciences, Inc.	2016-06-28	Not applicable
Epclusa	Sofosbuvir (150 mg/1) + Velpatasvir (37.5 mg/1)	Pellet	Oral	Gilead Sciences, Inc.	2021-06-10	Not applicable
Epclusa	Sofosbuvir (200 mg) + Velpatasvir (50 mg)		Oral	Gilead Sciences Ireland Uc	2022-06-08	Not applicable
Epclusa	Sofosbuvir (400 mg) + Velpatasvir (100 mg)	Tablet, film coated	Oral	Gilead Sciences Ireland Uc	2016-09-08	Not applicable
EPCLUSA TABLET 400MG/100MG	Sofosbuvir (400 mg) + Velpatasvir (100 mg)	Tablet, film coated	Oral	GILEAD SCIENCES SINGAPORE PTE. LTD.	2017-10-19	Not applicable

Chemical Identifiers

UNII: WJ6CA3ZU8B
CAS number: 1190307-88-0
InChI Key: TTZHDVOVKQGIBA-IQWMDFIBSA-N
InChI: 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
IUPAC Name: propan-2-yl (2S)-2-{[(S)-{[(2R,3R,4R,5R)-5-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy}(phenoxy)phosphoryl]amino}propanoate
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)OC1=CC=CC=C1

References

Synthesis Reference

Sofia MJ, Bao D, Chang W, Du J, Nagarathnam D, Rachakonda S, Reddy PG, Ross BS, Wang P, Zhang HR, Bansal S, Espiritu C, Keilman M, Lam AM, Steuer HM, Niu C, Otto MJ, Furman PA: Discovery of a beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-C-methyluridine nucleotide prodrug (PSI-7977) for the treatment of hepatitis C virus. J Med Chem. 2010 Oct 14;53(19):7202-18

General References

Asselah T: Sofosbuvir for the treatment of hepatitis C virus. Expert Opin Pharmacother. 2014 Jan;15(1):121-30. doi: 10.1517/14656566.2014.857656. Epub 2013 Nov 30. [Article]
Fung A, Jin Z, Dyatkina N, Wang G, Beigelman L, Deval J: Efficiency of incorporation and chain termination determines the inhibition potency of 2'-modified nucleotide analogs against hepatitis C virus polymerase. Antimicrob Agents Chemother. 2014 Jul;58(7):3636-45. doi: 10.1128/AAC.02666-14. Epub 2014 Apr 14. [Article]
Molina JM, Orkin C, Iser DM, Zamora FX, Nelson M, Stephan C, Massetto B, Gaggar A, Ni L, Svarovskaia E, Brainard D, Subramanian GM, McHutchison JG, Puoti M, Rockstroh JK: Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study. Lancet. 2015 Mar 21;385(9973):1098-106. doi: 10.1016/S0140-6736(14)62483-1. Epub 2015 Feb 4. [Article]
Simmonds P: Genetic diversity and evolution of hepatitis C virus--15 years on. J Gen Virol. 2004 Nov;85(Pt 11):3173-88. [Article]
Bagaglio S, Uberti-Foppa C, Morsica G: Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use. Drugs. 2017 May 12. doi: 10.1007/s40265-017-0753-x. [Article]
Myers RP, Shah H, Burak KW, Cooper C, Feld JJ: An update on the management of chronic hepatitis C: 2015 Consensus guidelines from the Canadian Association for the Study of the Liver. Can J Gastroenterol Hepatol. 2015 Jan-Feb;29(1):19-34. Epub 2015 Jan 13. [Article]
Naggie S, Cooper C, Saag M, Workowski K, Ruane P, Towner WJ, Marks K, Luetkemeyer A, Baden RP, Sax PE, Gane E, Santana-Bagur J, Stamm LM, Yang JC, German P, Dvory-Sobol H, Ni L, Pang PS, McHutchison JG, Stedman CA, Morales-Ramirez JO, Brau N, Jayaweera D, Colson AE, Tebas P, Wong DK, Dieterich D, Sulkowski M: Ledipasvir and Sofosbuvir for HCV in Patients Coinfected with HIV-1. N Engl J Med. 2015 Aug 20;373(8):705-13. doi: 10.1056/NEJMoa1501315. Epub 2015 Jul 21. [Article]
Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]
Denning J, Cornpropst M, Flach SD, Berrey MM, Symonds WT: Pharmacokinetics, safety, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor for hepatitis C virus, following single ascending doses in healthy subjects. Antimicrob Agents Chemother. 2013 Mar;57(3):1201-8. doi: 10.1128/AAC.01262-12. Epub 2012 Dec 21. [Article]
Xu S, Doehle B, Rajyaguru S, Han B, Barauskas O, Feng J, Perry J, Dvory-Sobol H, Svarovskaia ES, Miller MD, Mo H: In vitro selection of resistance to sofosbuvir in HCV replicons of genotype 1 to 6. Antivir Ther. 2017 Mar 1. doi: 10.3851/IMP3149. [Article]
Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [Article]
Hill A, Simmons B, Gotham D, Fortunak J: Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C. J Virus Erad. 2016 Jan 1;2(1):28-31. [Article]
Eltahla AA, Luciani F, White PA, Lloyd AR, Bull RA: Inhibitors of the Hepatitis C Virus Polymerase; Mode of Action and Resistance. Viruses. 2015 Sep 29;7(10):5206-24. doi: 10.3390/v7102868. [Article]
American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
FDA Approved Drug Products: Epclusa (sofosbuvir and velpatasvir) tablets or pellets for oral use [Link]
FDA Approved Drug Products: Harvoni (Ledipasvir and Sofosbuvir) tablets or pellets for oral use [Link]
FDA Approved Drug Products: Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) tablets for oral use [Link]
FDA Approved Drug Products: Sovaldi (sofosbuvir) tablets or pellets for oral use [Link]

External Links

KEGG Drug: D10366
PubChem Compound: 45375808
PubChem Substance: 175427164
ChemSpider: 26286922
BindingDB: 50239940
RxNav: 1484911
ChEBI: 85083
ChEMBL: CHEMBL1259059
ZINC: ZINC000100074252
PharmGKB: PA166122593
PDBe Ligand: WG6
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Sofosbuvir

PDB Entries

8e5b

MSDS

Download (616 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Chronic Hepatitis C Virus (HCV) Infection / People Who Inject Drugs	1
4	Active Not Recruiting	Treatment	Hepatitis C Virus (HCV) Infection / Injection Drug Use / Opioid Related Disorders	1
4	Completed	Basic Science	Cardiovascular Disease (CVD) / Hepatitis C Virus (HCV) Infection / Human Immunodeficiency Virus (HIV) Infections	1
4	Completed	Health Services Research	Chronic Hepatitis C Virus (HCV) Infection / Opioid Use Disorder (OUD)	1
4	Completed	Other	Coinfection, HIV / Hepatitis C Virus (HCV) Infection	1
4	Completed	Other	Hepatitis C Virus (HCV) Infection / Hepatocellular Carcinoma / Treatment Complications / Tumor Recurrence	1
4	Completed	Other	Hepatitis C Virus (HCV) Infection / Transplantation Disease Transmission	1
4	Completed	Treatment	Beta-Thalassemia / Hepatitis C Virus (HCV) Infection	1
4	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection	9
4	Completed	Treatment	Chronic Hepatitis C Virus (HCV) Infection / Chronic Obstructive Pulmonary Disease (COPD) / Heart Failure / Interstitial Lung Disease	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Tablet	Oral	400 MG
Granule	Oral
Pellet	Oral
Tablet	Oral
Tablet, film coated	Oral	90 mg
Tablet, film coated	Oral
Tablet, film coated	Oral	400 mg
Granule	Oral	150 MG
Granule	Oral	200 MG
Pellet	Oral	150 mg/1
Pellet	Oral	150 mg
Pellet	Oral	200 mg/1
Tablet	Oral
Tablet	Oral	200 mg
Tablet, film coated	Oral	200 mg/1
Tablet, film coated	Oral	200 MG
Tablet, film coated	Oral	400 mg/1
Tablet, film coated	Oral	400.0 mg
Tablet, film coated	Oral
Tablet, coated	Oral	400 mg
Tablet, coated	Oral

Prices

Not Available

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
US8841278	Yes	2014-09-23	2030-11-12
US7964580	Yes	2011-06-21	2029-09-26
US8334270	Yes	2012-12-18	2028-09-21
US8822430	Yes	2014-09-02	2030-11-12
US8633309	Yes	2014-01-21	2029-09-26
US8273341	Yes	2012-09-25	2030-11-12
US8618076	Yes	2013-12-31	2031-06-11
US8735372	Yes	2014-05-27	2028-09-21
US8580765	Yes	2013-11-12	2028-09-21
US8889159	Yes	2014-11-18	2029-09-26
US9085573	Yes	2015-07-21	2028-09-21
US9284342	Yes	2016-03-15	2031-03-13
US8088368	Yes	2012-01-03	2030-11-12
US9393256	Yes	2016-07-19	2033-03-14
US9511056	Yes	2016-12-06	2030-11-12
US9549941	Yes	2017-01-24	2029-09-26
US8940718	Yes	2015-01-27	2033-05-16
US8575135	Yes	2013-11-05	2034-05-05
US8921341	Yes	2014-12-30	2033-05-16
US9585906	No	2017-03-07	2028-03-21
US9296782	No	2016-03-29	2034-07-17
US9757406	Yes	2017-09-12	2034-07-30
US9868745	No	2018-01-16	2032-11-16
US10039779	Yes	2018-08-07	2034-07-30
US10086011	Yes	2018-10-02	2034-07-30
US10456414	No	2019-10-29	2032-09-14
US8957046	No	2015-02-17	2028-03-21
US10912814	No	2021-02-09	2037-06-01
US11116783	Yes	2021-09-14	2034-07-30
US11338007	Yes	2017-12-01	2037-12-01

Properties

State

Solid

Experimental Properties

Property	Value	Source
logP	1.62	FDA Label
pKa	9.3	FDA Label

Predicted Properties

Property	Value	Source
Water Solubility	0.824 mg/mL	ALOGPS
logP	1.63	ALOGPS
logP	1.28	Chemaxon
logS	-2.8	ALOGPS
pKa (Strongest Acidic)	9.7	Chemaxon
pKa (Strongest Basic)	-3.9	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	6	Chemaxon
Hydrogen Donor Count	3	Chemaxon
Polar Surface Area	152.73 Å²	Chemaxon
Rotatable Bond Count	11	Chemaxon
Refractivity	121.59 m³·mol^-1	Chemaxon
Polarizability	49.89 Å³	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	0	Chemaxon
Rule of Five	No	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	Yes	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Targets

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insights and accelerate drug research.

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Details1. RNA-dependent RNA-polymerase

Kind: Protein
Organism: Hepatitis C Virus
Pharmacological action: Yes
Actions: Inhibitor

General Function: Rna-directed rna polymerase activity
Specific Function: Not Available
Gene Name: NS5b
Uniprot ID: O39930
Uniprot Name: RNA-dependent RNA-polymerase
Molecular Weight: 65753.05 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Enzymes

Details1. Lysosomal protective protein

Kind: Protein
Organism: Not Available
Pharmacological action: Unknown
Actions: Substrate

General Function: Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
Specific Function: Carboxypeptidase activity
Gene Name: CTSA
Uniprot ID: P10619
Uniprot Name: Lysosomal protective protein
Molecular Weight: 54465.655 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Details2. Carboxylesterase

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Carboxylic ester hydrolase activity
Specific Function: Not Available
Gene Name: CES1A1a
Uniprot ID: Q6LAP9
Uniprot Name: Carboxylesterase
Molecular Weight: 1908.25 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Details3. Histidine triad nucleotide-binding protein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Protein kinase c binding
Specific Function: Hydrolyzes purine nucleotide phosphoramidates with a single phosphate group, including adenosine 5'monophosphoramidate (AMP-NH2), adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosin...
Gene Name: HINT1
Uniprot ID: P49773
Uniprot Name: Histidine triad nucleotide-binding protein 1
Molecular Weight: 13801.815 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Details4. UMP-CMP kinase

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Uridylate kinase activity
Specific Function: Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as...
Gene Name: CMPK1
Uniprot ID: P30085
Uniprot Name: UMP-CMP kinase
Molecular Weight: 22222.175 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Details5. Nucleoside diphosphate kinase A

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Substrate

General Function: Ribosomal small subunit binding
Specific Function: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-sit...
Gene Name: NME1
Uniprot ID: P15531
Uniprot Name: Nucleoside diphosphate kinase A
Molecular Weight: 17148.635 Da

References

Murakami E, Tolstykh T, Bao H, Niu C, Steuer HM, Bao D, Chang W, Espiritu C, Bansal S, Lam AM, Otto MJ, Sofia MJ, Furman PA: Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47. doi: 10.1074/jbc.M110.161802. Epub 2010 Aug 26. [Article]

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Tischer S, Fontana RJ: Drug-drug interactions with oral anti-HCV agents and idiosyncratic hepatotoxicity in the liver transplant setting. J Hepatol. 2014 Apr;60(4):872-84. doi: 10.1016/j.jhep.2013.11.013. Epub 2013 Nov 23. [Article]
Burgess S, Partovi N, Yoshida EM, Erb SR, Azalgara VM, Hussaini T: Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients. Ann Pharmacother. 2015 Jun;49(6):674-87. doi: 10.1177/1060028015576180. Epub 2015 Mar 13. [Article]

Details2. ATP-binding cassette sub-family G member 2

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

General Function: Xenobiotic-transporting atpase activity
Specific Function: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name: ABCG2
Uniprot ID: Q9UNQ0
Uniprot Name: ATP-binding cassette sub-family G member 2
Molecular Weight: 72313.47 Da

Drug created at January 02, 2014 04:48 / Updated at September 28, 2023 01:14

Sofosbuvir

Identification

Structure for Sofosbuvir (DB08934)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Targets

References

Enzymes

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References

References

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Transporters

References