Details of the Drug

General Information of Drug (ID: DMLSUWZ)

Drug Name
PSI-7977
Synonyms
1190307-88-0; SOVALDI; PSI 7977; GS-7977; GS 7977; UNII-WJ6CA3ZU8B; WJ6CA3ZU8B; CHEBI:85083; Sofosbuvir (PSI-7977, GS-7977); Hepcvir; Hepcinat; HSDB 8226; 2-((5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-ylmethoxy)phenoxyphosphorylamino)propionic acid isopropyl ester; Sofosbuvir [USAN:INN]; Resof; SoviHep; Sovaldi (TN); Sofosbuvir (JAN/USAN); Sofosbuvir(PSI-7977); GTPL7368; SCHEMBL2010114; CHEMBL1259059; AMMD00019; EX-A389; MolPort-028-720-482; isopropyl (2S)-2-[[[(2R,
Indication
Disease Entry ICD 11 Status REF
HCV 1-6 infection 1E51 Approved [1]
Hepatitis C virus infection 1E51.1 Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 529.5
Topological Polar Surface Area (xlogp) 1
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 11
Chemical Identifiers
Formula
C22H29FN3O9P
IUPAC Name
propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2,4-dioxopyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
Canonical SMILES
C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
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
InChIKey
TTZHDVOVKQGIBA-IQWMDFIBSA-N
Cross-matching ID
PubChem CID
45375808
ChEBI ID
CHEBI:85083
CAS Number
1190307-88-0
DrugBank ID
DB08934
TTD ID
D0D4YZ
INTEDE ID
DR1495
ACDINA ID
D00634

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B) TTMVBWH POLG_HCV1 Modulator [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Carboxylesterase 1 (CES1) DEB30C5 EST1_HUMAN Substrate [4]
Adenosine 5'-monophosphoramidase (HINT1) DEWJATF HINT1_HUMAN Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from PSI-7977 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Arn-509 DMT81LZ Major Accelerated clearance of PSI-7977 due to the transporter induction by Arn-509. Acute myeloid leukaemia [2A60] [24]
Erdafitinib DMI782S Moderate Decreased clearance of PSI-7977 due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [25]
Tucatinib DMBESUA Moderate Decreased clearance of PSI-7977 due to the transporter inhibition by Tucatinib. Breast cancer [2C60-2C6Y] [26]
PF-06463922 DMKM7EW Major Accelerated clearance of PSI-7977 due to the transporter induction by PF-06463922. Lung cancer [2C25] [24]
Lasmiditan DMXLVDT Moderate Decreased clearance of PSI-7977 due to the transporter inhibition by Lasmiditan. Migraine [8A80] [27]
Fostamatinib DM6AUHV Moderate Decreased clearance of PSI-7977 due to the transporter inhibition by Fostamatinib. Thrombocytopenia [3B64] [28]
⏷ Show the Full List of 6 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Carmellose sodium E00625 Not Available Disintegrant
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Talc E00520 16211421 Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
Water E00035 962 Solvent
⏷ Show the Full List of 8 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Sofosbuvir 400 mg tablet 400 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
2 2011 Pipeline of Pharmasset.
3 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
4 Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
5 Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23.
6 Absorption and cleavage of enalapril, a carboxyl ester prodrug, in the rat intestine: in vitro, in situ intestinal perfusion and portal vein cannulation models. Biopharm Drug Dispos. 2015 Sep;36(6):385-397.
7 Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
8 Effect of carboxylesterase 1 c.428G>A single nucleotide variation on the pharmacokinetics of quinapril and enalapril. Br J Clin Pharmacol. 2015 Nov;80(5):1131-8.
9 Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76.
10 Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
11 Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat. 2006 Dec;2(4):467-73.
12 Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
13 Pharmacogenomics of novel direct oral anticoagulants: newly identified genes and genetic variants. J Pers Med. 2019 Jan 17;9(1). pii: E7.
14 Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704.
15 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
16 Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
17 2011 Pipeline of Boehringer Ingelheim Pharma.
18 Valopicitabine dihydrochloride:a specific polymerase inhibitor of hepatitis C virus. Curr Opin Investig Drugs. 2007 Feb;8(2):150-8.
19 Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
20 Clinical pipeline report, company report or official report of Gilead (2011).
21 2011 Pipeline of Vertex.
22 All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11.
23 2011 Pipeline of Bristol-Myers Squibb.
24 Cerner Multum, Inc. "Australian Product Information.".
25 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
26 Product Information. Tukysa (tucatinib). Seattle Genetics Inc, Bothell, WA.
27 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
28 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.