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
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
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatChronic hepatitis c - genotype 3Combination Product in combination with: Voxilaprevir (DB12026), Velpatasvir (DB11613)•••••••••••••••••••••••••••• ••••• •••••••• •••••••••• ••••••• •••• •• ••• ••••••• •••••••••• •••••••••• ••••••• •• •••• •••••••••••••••
Used in combination to treatChronic hepatitis c - genotype 3Combination Product in combination with: Voxilaprevir (DB12026), Velpatasvir (DB11613)••••••••••••••••••••••••••• ••••••• •••• •• ••• ••••••• •••••••••• •••••••••• ••••••• •• •••• •••••••••••••••
Used in combination to treatChronic hepatitis c - genotype 3Regimen in combination with: Ribavirin (DB00811)•••••••••••••••••• •••••••••••••••••••• ••••• •••••••••••••• ••••••
Used in combination to treatChronic hepatitis c - genotype 3Regimen in combination with: Ribavirin (DB00811)•••••••••••••••••• •••••••••••••••• ••••••
Used in combination to treatChronic hepatitis c genotype 1Combination Product in combination with: Ribavirin (DB00811), Ledipasvir (DB09027)•••••••••••••••••• ••••••••••••••••••••••••• •••••• ••••••••••• ••••• •••••••••••••• ••••••
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.

TargetActionsOrganism
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

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.
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
AbemaciclibAbemaciclib may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
AbrocitinibThe serum concentration of Sofosbuvir can be increased when it is combined with Abrocitinib.
AceclofenacAceclofenac may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Sofosbuvir which could result in a higher serum level.
Food Interactions
  • Take with or without food.

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
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SovaldiPellet150 mgOralGilead Sciences Ireland Uc2020-12-22Not applicableEU flag
SovaldiTablet, film coated400 mgOralGilead Sciences Ireland Uc2016-09-08Not applicableEU flag
SovaldiPellet150 mg/1OralGilead Sciences, Inc.2019-08-28Not applicableUS flag
SovaldiTablet, film coated200 mgOralGilead Sciences Ireland Uc2020-12-22Not applicableEU flag
SovaldiTablet400 mgOralGilead Sciences2014-01-06Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
EpclusaSofosbuvir (150 mg/1) + Velpatasvir (37.5 mg/1)PelletOralGilead Sciences, Inc.2021-06-10Not applicableUS flag
EPCLUSASofosbuvir (400 MG) + Velpatasvir (100 MG)Tablet, film coatedOralGilead Sciences Ireland Uc2017-04-28Not applicableItaly flag
EpclusaSofosbuvir (200 mg) + Velpatasvir (50 mg)Tablet, film coatedOralGilead Sciences Ireland Uc2020-12-23Not applicableEU flag
EpclusaSofosbuvir (200 mg/1) + Velpatasvir (50 mg/1)PelletOralGilead Sciences, Inc.2021-06-10Not applicableUS flag
EpclusaSofosbuvir (200 mg) + Velpatasvir (50 mg)OralGilead Sciences Ireland Uc2022-06-08Not applicableEU flag

Categories

ATC Codes
J05AP08 — SofosbuvirJ05AP51 — Sofosbuvir and ledipasvirJ05AP55 — Sofosbuvir and velpatasvirJ05AP56 — Sofosbuvir, velpatasvir and voxilaprevir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Pyrimidine 2'-deoxyribonucleosides
Direct Parent
Pyrimidine 2'-deoxyribonucleosides
Alternative Parents
Alpha amino acid esters / Alanine and derivatives / Phosphoric diester monoamides / Phenoxy compounds / Pyrimidones / Hydropyrimidines / Organic phosphoramides / Vinylogous amides / Tetrahydrofurans / Heteroaromatic compounds
show 15 more
Substituents
Alanine or derivatives / Alcohol / Alkyl fluoride / Alkyl halide / Alpha-amino acid ester / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group
show 32 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, ring assembly, L-alanyl ester, phosphoramidate ester, nucleotide conjugate (CHEBI:85083)
Affected organisms
  • Hepatitis C Virus

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
  1. 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]
  2. 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]
  3. 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]
  4. Simmonds P: Genetic diversity and evolution of hepatitis C virus--15 years on. J Gen Virol. 2004 Nov;85(Pt 11):3173-88. [Article]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. Dusheiko G: Side effects of alpha interferon in chronic hepatitis C. Hepatology. 1997 Sep;26(3 Suppl 1):112S-121S. [Article]
  12. 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]
  13. 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]
  14. American Association for the Study of Liver Diseases; Infectious Diseases Society of America. HCV guidance. http://hcvguidelines.org. Accessed June 12, 2017. [Link]
  15. FDA Approved Drug Products: Epclusa (sofosbuvir and velpatasvir) tablets or pellets for oral use [Link]
  16. FDA Approved Drug Products: Harvoni (Ledipasvir and Sofosbuvir) tablets or pellets for oral use [Link]
  17. FDA Approved Drug Products: Vosevi (sofosbuvir, velpatasvir, and voxilaprevir) tablets for oral use [Link]
  18. FDA Approved Drug Products: Sovaldi (sofosbuvir) tablets or pellets for oral use [Link]
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 / 8fhs
MSDS
Download (616 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral400 MG
GranuleOral
PelletOral
TabletOral
Tablet, film coatedOral90 mg
Tablet, film coatedOral
Tablet, film coatedOral400 mg
GranuleOral150 MG
GranuleOral200 MG
PelletOral150 mg
PelletOral150 mg/1
PelletOral200 mg/1
TabletOral
TabletOral200 mg
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral200 MG
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral400.0 mg
Tablet, film coatedOral
Tablet, coatedOral400 mg
Tablet, coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US8841278Yes2014-09-232030-11-12US flag
US7964580Yes2011-06-212029-09-26US flag
US8334270Yes2012-12-182028-09-21US flag
US8822430Yes2014-09-022030-11-12US flag
US8633309Yes2014-01-212029-09-26US flag
US8273341Yes2012-09-252030-11-12US flag
US8618076Yes2013-12-312031-06-11US flag
US8735372Yes2014-05-272028-09-21US flag
US8580765Yes2013-11-122028-09-21US flag
US8889159Yes2014-11-182029-09-26US flag
US9085573Yes2015-07-212028-09-21US flag
US9284342Yes2016-03-152031-03-13US flag
US8088368Yes2012-01-032030-11-12US flag
US9393256Yes2016-07-192033-03-14US flag
US9511056Yes2016-12-062030-11-12US flag
US9549941Yes2017-01-242029-09-26US flag
US8940718Yes2015-01-272033-05-16US flag
US8575135Yes2013-11-052034-05-05US flag
US8921341Yes2014-12-302033-05-16US flag
US9585906No2017-03-072028-03-21US flag
US9296782No2016-03-292034-07-17US flag
US9757406Yes2017-09-122034-07-30US flag
US9868745No2018-01-162032-11-16US flag
US10039779Yes2018-08-072034-07-30US flag
US10086011Yes2018-10-022034-07-30US flag
US10456414No2019-10-292032-09-14US flag
US8957046No2015-02-172028-03-21US flag
US10912814No2021-02-092037-06-01US flag
US11116783Yes2021-09-142034-07-30US flag
US11338007Yes2017-12-012037-12-01US flag
US11707479Yes2014-07-302034-07-30US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.62FDA Label
pKa9.3FDA Label
Predicted Properties
PropertyValueSource
Water Solubility0.824 mg/mLALOGPS
logP1.63ALOGPS
logP1.28Chemaxon
logS-2.8ALOGPS
pKa (Strongest Acidic)9.7Chemaxon
pKa (Strongest Basic)-3.9Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area152.73 Å2Chemaxon
Rotatable Bond Count11Chemaxon
Refractivity121.59 m3·mol-1Chemaxon
Polarizability49.89 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01qc-9153860000-566637042b418ef6959d
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-2113490000-8fd65b2f5dc0ab6cc85e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03ea-6981110000-62010945ec5df55ccd49
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00uf-5130900000-06c850066d9d6c2473a5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0ae9-4950020000-6c8240a9e1c10dfb5f0d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-6931310000-b4c665d7dfa0220f5afc
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-205.17278
predicted
DeepCCS 1.0 (2019)
[M+H]+206.99768
predicted
DeepCCS 1.0 (2019)
[M+Na]+212.6035
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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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
  1. 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

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
  1. 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]
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
  1. 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]
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
  1. 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]
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
  1. 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]
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
  1. 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

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
  1. 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]
  2. 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]
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 March 19, 2024 11:06