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

General Information of Drug (ID: DR0871)
Drug Name
Indinavir sulfate
Synonyms
Indinavir [USAN:INN:BAN]; Indinavir [USAN]; Crixivan (TN); INDINAVIR SULPHATE; Indinavir (sulfate); Indinavir Sulfate [USAN]; Indinavir sulfate; Indinavir sulfate (USAN); L 735524; MK 639; (alphaR,gammaS,2S)-alpha-Benzyl-2-(tert-butylcarbamoyl)-gamma-hydroxy-N-((1S,2R)-2-hydroxy-1-indanyl)-4-(3-pyridylmethyl)-1-piperazinevaleramide sulfate (1:1) (salt); 157810-81-6; 771H53976Q; CHEBI:5899; DRG-0233; DSSTox_CID_24221; DSSTox_GSID_44221; DSSTox_RID_80126; HSDB 7158; IDV; UNII-771H53976Q; L-735524; indinavir; (1(1S,2R),5(S))-2,3,5-Trideoxy-N-(2,3-dihydro-2-hydroxy-1H-inden-1-yl)-5-(2-(((1,1-dimethylethyl)amino)carbonyl)-4-(3-pyridinylmethyl)-1-piperazinyl)-2-(phenylmethyl)-D-erythro-Pentonamide; 150378-17-9; 9MG78X43ZT; C36H47N5O4; Compound J; CHEBI:44032; N-[2(R)-HYDROXY-1(S)-INDANYL]-5-[(2(S)-TERTIARY BUTYLAMINOCARBONYL)-4(3-PYRIDYLMETHYL)PIPERAZINO]-4(S)-HYDROXY-2(R)-PHENYLMETHYLPENTANAMIDE; UNII-9MG78X43ZT
Indication Human immunodeficiency virus infection [ICD11: 1C60] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 711.9 Topological Polar Surface Area 201
Heavy Atom Count 50 Rotatable Bond Count 12
Hydrogen Bond Donor Count 6 Hydrogen Bond Acceptor Count 11
Cross-matching ID
PubChem CID
5462355
ChEBI ID
CHEBI:5899
CAS Number
157810-81-6
TTD Drug ID
D0V7CF
Formula
C36H49N5O8S
Canonical SMILES
CC(C)(C)NC(=O)C1CN(CCN1CC(CC(CC2=CC=CC=C2)C(=O)NC3C(CC4=CC=CC=C34)O)O)CC5=CN=CC=C5.OS(=O)(=O)O
InChI
1S/C36H47N5O4.H2O4S/c1-36(2,3)39-35(45)31-24-40(22-26-12-9-15-37-21-26)16-17-41(31)23-29(42)19-28(18-25-10-5-4-6-11-25)34(44)38-33-30-14-8-7-13-27(30)20-32(33)43;1-5(2,3)4/h4-15,21,28-29,31-33,42-43H,16-20,22-24H2,1-3H3,(H,38,44)(H,39,45);(H2,1,2,3,4)/t28-,29+,31+,32-,33+;/m1./s1
InChIKey
NUBQKPWHXMGDLP-BDEHJDMKSA-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
Indinavir sulfate metabolite M1 DM000978
118737587
Conjugation - Glucuronidation 1 [7]
Indinavir sulfate metabolite M3 DM000977
10394233
Oxidation - Hydroxylation 1 [7]
Indinavir sulfate metabolite M4a DM000973
101918262
Oxidation - Oxidation 1 [7]
Indinavir sulfate metabolite M4b DM000979
101918263
Oxidation - Hydroxylation 1 [7]
Indinavir sulfate metabolite M6 DM000974
5479517
Oxidation - N-Depyridomethylation 1 [7] , [8]
Niraparib metabolite M1 DM000978 N. A. Conjugation - Glucuronidation 1 [7]
Indinavir sulfate metabolite M2 DM000976
101918261
Oxidation - Hydroxylation 2 [7]
Indinavir sulfate metabolite M3 DM000977
10394233
Oxidation - Oxidation 2 [7]
Indinavir sulfate metabolite M5 DM000975
101918264
Oxidation - Hydroxylation 2 [7]
Indinavir sulfate metabolite M5 DM000975
101918264
Oxidation - N-Depyridomethylation 2 [7]
Indinavir sulfate metabolite M6 DM000974
5479517
Oxidation - N-Depyridomethylation 2 [7]
Indinavir sulfate metabolite M5 DM000975
101918264
Oxidation - N-Depyridomethylation 3 [7]
Indinavir sulfate metabolite M5 DM000975
101918264
Oxidation - Hydroxylation 3 [7]
⏷ Show the Full List of 13  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001191 Indinavir sulfate Indinavir sulfate metabolite M4a Oxidation - Oxidation CYP3A4 [7]
MR001192 Indinavir sulfate Indinavir sulfate metabolite M6 Oxidation - N-Depyridomethylation CYP3A4 [7], [8]
MR001193 Indinavir sulfate Indinavir sulfate metabolite M3 Oxidation - Hydroxylation CYP3A4 [7]
MR001194 Indinavir sulfate Indinavir sulfate metabolite M1 Conjugation - Glucuronidation Unclear [7]
MR001195 Indinavir sulfate Indinavir sulfate metabolite M4b Oxidation - Hydroxylation CYP3A4 [7]
MR001190 Indinavir sulfate metabolite M3 Indinavir sulfate metabolite M3 Oxidation - Oxidation CYP3A4 [7]
MR001185 Indinavir sulfate metabolite M4a Indinavir sulfate metabolite M6 Oxidation - N-Depyridomethylation CYP3A4 [7]
MR001186 Indinavir sulfate metabolite M4a Indinavir sulfate metabolite M2 Oxidation - Hydroxylation CYP3A4 [7]
MR001188 Indinavir sulfate metabolite M2 Indinavir sulfate metabolite M5 Oxidation - N-Depyridomethylation CYP3A4 [7]
MR001189 Indinavir sulfate metabolite M3 Indinavir sulfate metabolite M5 Oxidation - N-Depyridomethylation CYP3A4 [7]
MR001187 Indinavir sulfate metabolite M6 Indinavir sulfate metabolite M5 Oxidation - Hydroxylation CYP3A4 [7]
⏷ Show the Full List of 11 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[6]
References
1 Indinavir Sulfate was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. J Pharm Sci. 1998 Oct;87(10):1184-9.
3 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
4 Enzymes in addition to CYP3A4 and 3A5 mediate N-demethylation of dextromethorphan in human liver microsomes. Biopharm Drug Dispos. 1999 Oct;20(7):341-6.
5 Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85.
6 Inhibition of bilirubin metabolism induces moderate hyperbilirubinemia and attenuates ANG II-dependent hypertension in mice. Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R738-43.
7 Hepatic and intestinal metabolism of indinavir, an HIV protease inhibitor, in rat and human microsomes. Major role of CYP3A. Biochem Pharmacol. 1997 Apr 25;53(8):1187-95.
8 Involvement of CYP3A4 and MDR1 in altered metabolism and transport of indinavir in 1,25(OH)(2)D(3)-treated Caco-2 cells. Eur J Pharm Sci. 2023 Apr 1;183:106396. doi: 10.1016/j.ejps.2023.106396.

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