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

General Information of Drug (ID: DR5343)
Drug Name
Tucatinib
Synonyms
Irbinitinib; 937263-43-9; ONT-380; UNII-234248D0HH; 234248D0HH; N6-(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)-N4-(3-methyl-4-((1,2,4)triazolo(1,5-a)pyridin-7-yloxy)phenyl)quinazoline-4,6-diamine; 4,6-Quinazolinediamine, N6-(4,5-dihydro-4,4-dimethyl-2-oxazolyl)-N4-(3-methyl-4-((1,2,4)triazolo(1,5-a)pyridin-7-yloxy)phenyl)-; ONT 380; 4,6-QuinazolinediaMine, N6-(4,5-dihydro-4,4-diMethyl-2-oxazolyl)-N4-[3-Methyl-4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)phenyl]-; Tucatinib [USAN:INN]; 6-DIAMINE
Indication HER2-positive breast cancer [ICD11: 2C60-2C6Y] Approved [1]
Stomach cancer [ICD11: ICD11: 2B72] Phase 2/3 [2]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 480.5 Topological Polar Surface Area 111
Heavy Atom Count 36 Rotatable Bond Count 6
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
51039094
CAS Number
937263-43-9
TTD Drug ID
D09GRX
Formula
C26H24N8O2
Canonical SMILES
CC1=C(C=CC(=C1)NC2=NC=NC3=C2C=C(C=C3)NC4=NC(CO4)(C)C)OC5=CC6=NC=NN6C=C5
InChI
InChI=1S/C26H24N8O2/c1-16-10-17(5-7-22(16)36-19-8-9-34-23(12-19)28-15-30-34)31-24-20-11-18(4-6-21(20)27-14-29-24)32-25-33-26(2,3)13-35-25/h4-12,14-15H,13H2,1-3H3,(H,32,33)(H,27,29,31)
InChIKey
SDEAXTCZPQIFQM-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
Tucatinib metabolite M1 DM016249
66937323
Oxidation - Hydroxylation 1 [4]
Tucatinib metabolite M20 DM017139 N. A. Oxidation - Oxidation 1 [4]
Tucatinib metabolite M23 DM017146 N. A. Oxidation - Oxidation 1 [4]
Tucatinib metabolite M25 DM017144 N. A. Oxidation - Oxazoline ring oxidation 1 [4]
Tucatinib metabolite M31 DM017145 N. A. Oxidation - Dehydrogenation 1 [4]
Tucatinib metabolite M18 DM017142 N. A. Unclear - Unclear 2 [4]
Tucatinib metabolite M19 DM017143 N. A. Unclear - Unclear 2 [4]
Tucatinib metabolite M22 DM017140 N. A. Unclear - Unclear 2 [4]
Tucatinib metabolite M28 DM017141 N. A. Unclear - Unclear 3 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR008163 Tucatinib Tucatinib metabolite M20 Oxidation - Oxidation CYP3A4 [4]
MR008168 Tucatinib Tucatinib metabolite M1 Oxidation - Hydroxylation CYP2C8 [4]
MR008171 Tucatinib Tucatinib metabolite M25 Oxidation - Oxazoline ring oxidation Unclear [4]
MR008173 Tucatinib Tucatinib metabolite M31 Oxidation - Dehydrogenation Unclear [4]
MR008174 Tucatinib Tucatinib metabolite M23 Oxidation - Oxidation CYP3A4 ... [4]
MR008169 Tucatinib metabolite M1 Tucatinib metabolite M18 Unclear - Unclear Unclear [4]
MR008170 Tucatinib metabolite M1 Tucatinib metabolite M19 Unclear - Unclear Unclear [4]
MR008164 Tucatinib metabolite M20 Tucatinib metabolite M22 Unclear - Unclear Unclear [4]
MR008166 Tucatinib metabolite M20 Tucatinib metabolite M18 Unclear - Unclear Unclear [4]
MR008172 Tucatinib metabolite M25 Tucatinib metabolite M19 Unclear - Unclear Unclear [4]
MR008167 Tucatinib metabolite M18 Tucatinib metabolite M28 Unclear - Unclear Unclear [4]
MR008165 Tucatinib metabolite M22 Tucatinib metabolite M28 Unclear - Unclear Unclear [4]
⏷ Show the Full List of 12 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
[3]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
References
1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2 ClinicalTrials.gov (NCT04499924) Tucatinib, Trastuzumab, Ramucirumab, and Paclitaxel Versus Paclitaxel and Ramucirumab in Previously Treated HER2+ Gastroesophageal Cancer (MOUNTAINEER-02). U.S. National Institutes of Health.
3 Pharmacokinetics and drug interactions of eslicarbazepine acetate Epilepsia. 2012 Jun;53(6):935-46. doi: 10.1111/j.1528-1167.2012.03519.x.
4 Elimination of tucatinib, a small molecule kinase inhibitor of HER2, is primarily governed by CYP2C8 enantioselective oxidation of gem-dimethyl

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