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

General Information of Drug (ID: DR0403)
Drug Name
Dabrafenib mesylate
Synonyms
Dabrafenib (Mesylate); Dabrafenib Mesylate (GSK-2118436); Dabrafenib Mesylate (GSK-2118436B); Dabrafenib mesylate; Dabrafenib mesylate (USAN); Dabrafenib mesylate [USAN]; Dabrafenib methanesulfonate; METHANE SULFONATE SALT; Tafinlar (TN); Taflinar; 1195768-06-9; B6DC89I63E; CHEBI:75048; GSK 2118436B; GSK-2118436A; GSK-2118436B; GSK2118436 Methane sulfonate salt; GSK2118436B; N-(3-(5-(2-aminopyrimidin-4-yl)-2-(tert-butyl)thiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide methanesulfonate; UNII-B6DC89I63E
Indication Melanoma [ICD11: 2C30] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 615.7 Topological Polar Surface Area 210
Heavy Atom Count 40 Rotatable Bond Count 6
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 14
Cross-matching ID
PubChem CID
44516822
ChEBI ID
CHEBI:75048
CAS Number
1195768-06-9
TTD Drug ID
D05ROI
Formula
C24H24F3N5O5S3
Canonical SMILES
CC(C)(C)C1=NC(=C(S1)C2=NC(=NC=C2)N)C3=C(C(=CC=C3)NS(=O)(=O)C4=C(C=CC=C4F)F)F.CS(=O)(=O)O
InChI
1S/C23H20F3N5O2S2.CH4O3S/c1-23(2,3)21-30-18(19(34-21)16-10-11-28-22(27)29-16)12-6-4-9-15(17(12)26)31-35(32,33)20-13(24)7-5-8-14(20)25;1-5(2,3)4/h4-11,31H,1-3H3,(H2,27,28,29);1H3,(H,2,3,4)
InChIKey
YKGMKSIHIVVYKY-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
Hydroxy-dabrafenib DM006151
57989740
Oxidation - Aliphatic hydroxylation 1 [4] , [5] , [6]
Carboxy-dabrafenib DM006152
57989831
Oxidation - Oxidationn 2 [4]
Desmethyl-dabrafenib DM006153
58345847
Oxidation - Decarboxylation 3 [4]
Dabrafenib mesylate Metabolite M26 DM006156 N. A. Unclear 4 [4]
Dabrafenib mesylate Metabolite M28 DM006157 N. A. Unclear 4 [4]
Dabrafenib mesylate Metabolite M29 DM006158 N. A. Unclear 4 [4]
M30-Dabrafenib DM006154 N. A. Oxidation - Oxidationn 4 [4]
M31-Dabrafenib DM006155
132502698
Oxidation - Oxidationn 4 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006597 Dabrafenib mesylate Hydroxy-dabrafenib Oxidation - Aliphatic hydroxylation Unclear [4], [5], [6]
MR006598 Hydroxy-dabrafenib Carboxy-dabrafenib Oxidation - Oxidationn Unclear [4]
MR006599 Carboxy-dabrafenib Desmethyl-dabrafenib Oxidation - Decarboxylation Unclear [4]
MR006600 Desmethyl-dabrafenib M30-Dabrafenib Oxidation - Oxidationn Unclear [4]
MR006601 Desmethyl-dabrafenib M31-Dabrafenib Oxidation - Oxidationn CYP3A4 ... [4]
MR006603 Dabrafenib mesylate Metabolite M26 Dabrafenib mesylate Metabolite M28 Unclear Unclear [4]
MR006604 Dabrafenib mesylate Metabolite M28 Dabrafenib mesylate Metabolite M29 Unclear Unclear [4]
MR006602 M31-Dabrafenib Dabrafenib mesylate Metabolite M26 Unclear CYP3A4 [4]
⏷ Show the Full List of 8 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
References
1 Dabrafenib Mesylate was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
3 Physiologically based pharmacokinetic modeling to identify physiological and molecular characteristics driving variability in drug exposure. Clin Pharmacol Ther. 2018 Dec;104(6):1219-1228.
4 Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation
5 Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib
6 Prediction of the Transporter-Mediated Drug-Drug Interaction Potential of Dabrafenib and Its Major Circulating Metabolites

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