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

General Information of Drug (ID: DR1142)
Drug Name
Nevirapine
Synonyms
Nevirapine (Viramune); Viramune; Viramune XR; nevirapine; 11-CYCLOPROPYL-5,11-DIHYDRO-4-METHYL-6H-DIPYRIDO[3,2-B:2',3'-E][1,4]DIAZEPIN-6-ONE; BI-RG 587; BI-RG-587; BIRG 0587; BIRG-0587; 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[2,3-e:3',2'-b][1,4]diazepin-6-one; 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one; 11-Cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido(3,2-b:2',3'-e)(1,4)diazepin-6-one; 129618-40-2; 99DK7FVK1H; CHEMBL57; HSDB 7164; NEV; NSC 641530; NVP; UNII-99DK7FVK1H
Indication Human immunodeficiency virus infection [ICD11: 1C60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 266.3 Topological Polar Surface Area 58.1
Heavy Atom Count 20 Rotatable Bond Count 1
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 4
Cross-matching ID
PubChem CID
4463
PubChem SID
9472 ; 500792 ; 597607 ; 601303 ; 819817 ; 823573 ; 823576 ; 826050 ; 826057 ; 826059 ; 826060 ; 832211 ; 832214 ; 833983 ; 865943 ; 866527 ; 5596797 ; 7847501 ; 7889356 ; 7889505 ; 7980115 ; 8031304 ; 8152750 ; 12014582 ; 14716699 ; 14716702 ; 14872507 ; 17388862 ; 24721613 ; 26718578 ; 26719643 ; 29223558 ; 46386569 ; 46393424 ; 46394249 ; 46506789 ; 48425381 ; 49718173 ; 49856363 ; 50086444 ; 50622552 ; 53789571 ; 56313692 ; 56313770 ; 57322283 ; 81093307 ; 85173516 ; 92308419 ; 92712790 ; 93166484
ChEBI ID
CHEBI:63613
CAS Number
129618-40-2
TTD Drug ID
D0O2EM
Formula
C15H14N4O
Canonical SMILES
CC1=C2C(=NC=C1)N(C3=C(C=CC=N3)C(=O)N2)C4CC4
InChI
1S/C15H14N4O/c1-9-6-8-17-14-12(9)18-15(20)11-3-2-7-16-13(11)19(14)10-4-5-10/h2-3,6-8,10H,4-5H2,1H3,(H,18,20)
InChIKey
NQDJXKOVJZTUJA-UHFFFAOYSA-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
12-hydroxynevirapine DM002160
453338
Oxidation - Hydroxylation 1 [9] , [10] , [2]
2-hydroxynevirapine DM002164
10850461
Oxidation - 2-Hydroxylation 1 [9] , [10]
3-hydroxynevirapine DM002168
10978907
Oxidation - 3-Hydroxylation 1 [11]
8-hydroxynevirapine DM002166
10755325
Oxidation - 8-Hydroxylation 1 [11]
12-hydroxynevirapine glucuronide metabolite DM002163
131769925
Unclear 2 [10]
12-sulphoxy-nevirapine DM002161 N. A. Unclear 2 [10]
2-hydroxynevirapine glucuronide metabolite DM002165
131769929
Conjugation - Glucuronidation 2 [9] , [10]
3-hydroxynevirapine glucuronide metabolite DM002169
131769937
Conjugation - Glucuronidation 2 [11]
4-carboxynevirapine DM002162
10709035
Unclear 2 [10]
8-hydroxynevirapine glucuronide metabolite DM002167
131770041
Conjugation - Glucuronidation 2 [11]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR003269 Nevirapine 12-hydroxynevirapine Oxidation - Hydroxylation CYP3A4 ... [9], [10], [2]
MR003270 Nevirapine 2-hydroxynevirapine Oxidation - 2-Hydroxylation CYP3A4 ... [9], [10]
MR003271 Nevirapine 8-hydroxynevirapine Oxidation - 8-Hydroxylation CYP3A4 ... [11]
MR003272 Nevirapine 3-hydroxynevirapine Oxidation - 3-Hydroxylation CYP2B6 [11]
MR003263 12-hydroxynevirapine 12-sulphoxy-nevirapine Unclear ULT [10]
MR003264 12-hydroxynevirapine 4-carboxynevirapine Unclear Unclear [10]
MR003265 12-hydroxynevirapine 12-hydroxynevirapine glucuronide metabolite Unclear UGT [10]
MR003266 2-hydroxynevirapine 2-hydroxynevirapine glucuronide metabolite Conjugation - Glucuronidation UGT [9], [10]
MR003268 3-hydroxynevirapine 3-hydroxynevirapine glucuronide metabolite Conjugation - Glucuronidation UGT [11]
MR003267 8-hydroxynevirapine 8-hydroxynevirapine glucuronide metabolite Conjugation - Glucuronidation UGT [11]
⏷ Show the Full List of 10 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[3]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[5]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[6]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[6]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[3]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[7]
Sulfotransferase (SULT) DMEN061 . Not Available Not Available [2]
UDP-glucuronosyltransferase 2A1 (UGT2A1) DME0622 Homo sapiens
UD2A1_HUMAN
2.4.1.17
[2]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [8]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [8]
⏷ Show the Full List of 12  DME(s)
References
1 Nevirapine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Sulfation of 12-hydroxy-nevirapine by human SULTs and the effects of genetic polymorphisms of SULT1A1 and SULT2A1. Biochem Pharmacol. 2022 Oct;204:115243. doi: 10.1016/j.bcp.2022.115243.
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 RAT CYP3A and CYP2B1/2 were not associated with nevirapine-induced hepatotoxicity. Methods Find Exp Clin Pharmacol. 2006 Sep;28(7):423-31.
5 Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol. 2001 Jan;41(1):85-91.
6 Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999 Dec;27(12):1488-95.
7 Helices F-G are important for the substrate specificities of CYP3A7. Drug Metab Dispos. 2007 Mar;35(3):484-92.
8 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
9 Disposition and biotransformation of the antiretroviral drug nevirapine in humans Drug Metab Dispos. 1999 Aug;27(8):895-901.
10 Differences in nevirapine biotransformation as a factor for its sex-dependent dimorphic profile of adverse drug reactions J Antimicrob Chemother. 2014 Feb;69(2):476-82. doi: 10.1093/jac/dkt359.
11 U. S. FDA Label -Nevirapine

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