Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMLSUWZ)

• Drug Name: PSI-7977 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 45375808
  ChEBI ID: CHEBI:85083
  CAS Number: CAS 1190307-88-0
  TTD Drug ID: DMLSUWZ
  INTEDE Drug ID: DR1495
  ACDINA Drug ID: D00634

Molecule-Related Drug Atlas

Drug(s) Targeting Hepatitis C virus RNA-directed RNA polymerase (HCV NS5B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Setrobuvir	DMTNDM2	Hepatitis C virus infection	1E51.1	Phase 2	[5]
BI 207127	DMMSGAT	Hepatitis C virus infection	1E51.1	Phase 2	[6]
Valopicitabine dihydrochloride	DMFWZ2U	Virus infection	1A24-1D9Z	Phase 2	[7]
INX-189	DMSTJ6Q	Hepatitis C virus infection	1E51.1	Phase 2	[8]
Tegobuvir	DM6YI5T	Hepatitis C virus infection	1E51.1	Phase 2	[9]
VX-759	DMJUSM8	Hepatitis C virus infection	1E51.1	Phase 2	[10]
VX-135	DMZ3FE8	Hepatitis C virus infection	1E51.1	Phase 2	[11]
VX-222	DMO3U4W	Hepatitis C virus infection	1E51.1	Phase 2	[10]
BMS 791325	DMKH4PI	Hepatitis C virus infection	1E51.1	Phase 2	[12]
Filibuvir	DMNSYXB	Hepatitis C virus infection	1E51.1	Phase 2	[13]

Drug(s) Metabolized By Carboxylesterase 1 (CES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[14]
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[15]
Candesartan	DMRK8OT	Chronic heart failure	BD1Z	Approved	[16]
Salbutamol	DMN9CWF	Acute asthma	CA23	Approved	[17]
Methylphenidate	DM7SJD6	Attention deficit hyperactivity disorder	6A05.Z	Approved	[18]
Rufinamide	DMWE60C	Epilepsy	8A60-8A68	Approved	[19]
Dexmethylphenidate	DMUQE2A	Attention deficit hyperactivity disorder	6A05.Z	Approved	[20]
MK-4827	DMLYGH4	Ovarian cancer	2C73	Phase 3	[21]
Dabigatran etexilate	DMRDZ4X	Venous thromboembolism	BD72	Phase 3	[22]
Pradaxa	DM2ZYX9	Stroke	8B20	Phase 3	[23]

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]

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] Clinical pipeline report, company report or official report of Anadys Pharmaceuticals (2011).
• [6] 2011 Pipeline of Boehringer Ingelheim Pharma.
• [7] Valopicitabine dihydrochloride:a specific polymerase inhibitor of hepatitis C virus. Curr Opin Investig Drugs. 2007 Feb;8(2):150-8.
• [8] Clinical pipeline report, company report or official report of Bristol-Myers Squibb.
• [9] Clinical pipeline report, company report or official report of Gilead (2011).
• [10] 2011 Pipeline of Vertex.
• [11] All-oral HCV therapies near approval. Nat Rev Drug Discov. 2013 Jun;12(6):409-11.
• [12] 2011 Pipeline of Bristol-Myers Squibb.
• [13] Clinical pipeline report, company report or official report of Pfizer (2011).
• [14] 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.
• [15] 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.
• [16] Different hydrolases involved in bioactivation of prodrug-type angiotensin receptor blockers: carboxymethylenebutenolidase and carboxylesterase 1. Drug Metab Dispos. 2013 Nov;41(11):1888-95.
• [17] 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.
• [18] Methylphenidate is stereoselectively hydrolyzed by human carboxylesterase CES1A1. J Pharmacol Exp Ther. 2004 Aug;310(2):469-76.
• [19] Investigation of the metabolism of rufinamide and its interaction with valproate. Drug Metab Lett. 2011 Dec;5(4):280-9.
• [20] Dexmethylphenidate hydrochloride in the treatment of attention deficit hyperactivity disorder. Neuropsychiatr Dis Treat. 2006 Dec;2(4):467-73.
• [21] Summary of FDA-approved anticancer cytotoxic drugs at May 2019.
• [22] Pharmacogenomics of novel direct oral anticoagulants: newly identified genes and genetic variants. J Pers Med. 2019 Jan 17;9(1). pii: E7.
• [23] 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.