Details of the Drug Metabolized by Drug-Metabolizing Enzyme (DME)

General Information of Drug (ID: DR1495)
Drug Name
Sofosbuvir
Prodrug Info Sofosbuvir is the prodrug of GS-331007-TP
Synonyms
Sofosbuvir (JAN/USAN); Sofosbuvir (PSI-7977, GS-7977); Sofosbuvir [USAN:INN]; Sofosbuvir(PSI-7977); Sovaldi (TN); SoviHep; WJ6CA3ZU8B; AMMD00019; Hepcinat; Hepcvir; PSI 7977; PSI-7977; SCHEMBL2010114; SOFOSBUVIR; SOVALDI; psi-7977-gs-7977; 1190307-88-0; 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; CHEBI:85083; CHEMBL1259059; EX-A389; GS 7977; GS-7977; GTPL7368; HSDB 8226; Resof; UNII-WJ6CA3ZU8B
Indication Viral hepatitis [ICD11: 1E51] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 529.5 Topological Polar Surface Area 153
Heavy Atom Count 36 Rotatable Bond Count 11
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 11
Cross-matching ID
PubChem CID
45375808
PubChem SID
93367218 ; 120288070 ; 123086722 ; 136350055 ; 141294064 ; 152258620 ; 160647455 ; 165245625 ; 172232459 ; 175428457 ; 178103940 ; 198982808 ; 206711582 ; 223715859 ; 228166432 ; 241383586 ; 242982572 ; 249625858 ; 249807077 ; 249816415 ; 251963215 ; 252155260 ; 252166959
ChEBI ID
CHEBI:85083
CAS Number
1190307-88-0
TTD Drug ID
D0D4YZ
Formula
C22H29FN3O9P
Canonical SMILES
CC(C)OC(=O)C(C)NP(=O)(OCC1C(C(C(O1)N2C=CC(=O)NC2=O)(C)F)O)OC3=CC=CC=C3
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
The Metabolic Roadmap of This Drug
The Full List of Drug Metabolites (DM) of This Drug
DM Name DM ID PubChem ID Reaction DM Level REF
GS-56650 DM016999 N. A. Unclear 1 [3] , [2]
MetX DM017000 N. A. Unclear 1 [5]
GS-331007-MP DM017001 N. A. Unclear 2 [5]
GS-606965 DM006357
23725126
Unclear 2 [3] , [2]
GS-331007 DM015746
11311503
Unclear 3 [5]
GS-331007-TP DM017002 N. A. Unclear 3 [5]
GS-461203 DM006358
23725128
Unclear 3 [3] , [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR013663 Sofosbuvir GS-56650 Unclear CES1 ... [3], [2]
MR013666 Sofosbuvir MetX Unclear CES1 ... [5]
MR013664 GS-56650 GS-606965 Unclear HINT1 [3], [2]
MR013667 MetX GS-331007-MP Unclear HINT1 [5]
MR013668 GS-331007-MP GS-331007-TP Unclear CMPK1 ... [5]
MR013669 GS-331007-MP GS-331007 Unclear Unclear [5]
MR013665 GS-606965 GS-461203 Unclear CMPK1 [3], [2]
⏷ Show the Full List of 7 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Adenosine 5'-monophosphoramidase (HINT1) DME0215 Homo sapiens
HINT1_HUMAN
3.2.1.45
[2]
Adenosine 5'-monophosphoramidase (HINT1) DME0215 Homo sapiens
HINT1_HUMAN
3.2.1.45
[3]
Carboxylesterase 1 (CES1) DME0054 Homo sapiens
EST1_HUMAN
3.1.1.1
[2]
Catalase (CAT) DME0090 Homo sapiens
CATA_HUMAN
1.11.1.6
[3]
Catechol 1,2-dioxygenase (catA) DMEN385 . Not Available Not Available [2]
Cathepsin A (CTSA) DME0071 Homo sapiens
PPGB_HUMAN
3.4.16.5
[2]
Nucleoside diphosphate kinase A (NME1) DMEN002 Homo sapiens
NDKA_HUMAN
2.7.1.30
[4]
Nucleoside diphosphate kinase A (NME1) DMEN002 Homo sapiens
NDKA_HUMAN
2.7.1.30
[5]
Uridine/cytidine monophosphate kinase (UMPK) DME0456 Homo sapiens
KCY_HUMAN
2.7.4.14
[5]
⏷ Show the Full List of 9  DME(s)
References
1 Sofosbuvir was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Mechanism of activation of PSI-7851 and its diastereoisomer PSI-7977. J Biol Chem. 2010 Nov 5;285(45):34337-47.
3 Pharmacokinetics, safety, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor for hepatitis C virus, following single ascending doses in healthy subjects
4 Effects of rifampin, itraconazole and esomeprazole on the pharmacokinetics of alisertib, an investigational aurora a kinase inhibitor in patients with advanced malignancies. Invest New Drugs. 2018 Apr;36(2):248-258. doi: 10.1007/s10637-017-0499-z.
5 Species differences in liver accumulation and metabolism of nucleotide prodrug sofosbuvir

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