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

General Information of Drug (ID: DR0526)
Drug Name
Dolutegravir sodium
Synonyms
Dolutegravir (sodium); Dolutegravir Sodium ( API); GSK 1349572A; GSK-1349572A; GSK1349572 sodiuM salt; GSK1349572A; Sodium (4R,12aS)-9-((2,4-difluorobenzyl)carbamoyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate;Sodium (4R,12aS)-9-((2,4-difluorobenzyl)carbamoyl)-4-methyl-6,8-dioxo-3,4,6,8,12,12a-hexahydro-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazin-7-olate; UNII-1Q1V9V5WYQ; 1051375-19-9; 1Q1V9V5WYQ; CHEBI:76007; DOLUTEGRAVIR SODIUM
Indication Human immunodeficiency virus infection [ICD11: 1C60] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 441.4 Topological Polar Surface Area 102
Heavy Atom Count 31 Rotatable Bond Count 3
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
46216142
ChEBI ID
CHEBI:76007
CAS Number
1051375-19-9
TTD Drug ID
D00YZD
Formula
C20H18F2N3NaO5
Canonical SMILES
CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)[O-].[Na+]
InChI
1S/C20H19F2N3O5.Na/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22;/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28);/q;+1/p-1/t10-,15+;/m1./s1
InChIKey
UGWJRRXTMKRYNK-VSLILLSYSA-M
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
Defluorinated and gutathione conjugated form of dolutegravir (M4.1) DM006172 N. A. Multi-steps Reaction - Glutathione conjugation; oxidative defluorination 1 [2]
Defluorinated and gutathione conjugated form of dolutegravir (M4.2) DM006173 N. A. Multi-steps Reaction - Glutathione conjugation; oxidative defluorination 1 [2]
Ether glucuronide dolutegravir (M2) DM006171 N. A. Conjugation - Glucuronidation 1 [2]
Hydroxilated form of dolutegravir (M3) DM006168 N. A. Oxidation - Hydrolyzationn 1 [2]
2,4- difluorobenzaldehyde (M5 dolutegravir) DM006169
91867
Hydrolysis - Hydrolysis 2 [2]
Hydrolized form of dolutegravir (M1) DM006170
142733905
Hydrolysis - Hydrolysis 2 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006614 Dolutegravir sodium Hydroxilated form of dolutegravir (M3) Oxidation - Hydrolyzationn CYP3A4 [2]
MR006617 Dolutegravir sodium Ether glucuronide dolutegravir (M2) Conjugation - Glucuronidation UGT1A1 ... [2]
MR006618 Dolutegravir sodium Defluorinated and gutathione conjugated form of dolutegravir (M4.1) Multi-steps Reaction - Glutathione conjugation; oxidative defluorination Unclear [2]
MR006619 Dolutegravir sodium Defluorinated and gutathione conjugated form of dolutegravir (M4.2) Multi-steps Reaction - Glutathione conjugation; oxidative defluorination Unclear [2]
MR006615 Hydroxilated form of dolutegravir (M3) 2,4- difluorobenzaldehyde (M5 dolutegravir) Hydrolysis - Hydrolysis CYP1A1 ... [2]
MR006616 Hydroxilated form of dolutegravir (M3) Hydrolized form of dolutegravir (M1) Hydrolysis - Hydrolysis CYP1A1 ... [2]
⏷ Show the Full List of 6 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1B1 (CYP1B1) DME0023 Homo sapiens
CP1B1_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[2]
⏷ Show the Full List of 6  DME(s)
References
1 Dolutegravir Sodium was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans
3 Mechanisms of action, pharmacology and interactions of dolutegravir. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:2-8.

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