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

General Information of Drug (ID: DR1401)
Drug Name
Regorafenib
Synonyms
Regorafenib; Regorafenib (BAY 73-4506); Regorafenibum; Stivarga; Stivarga (TN); 24T2A1DOYB; 4-(4-(3-(4-Chloro-3-(trifluoromethyl)phenyl)ureido)-3-fluorophenoxy)-N-methylpicolinamide; 4-[4-({[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide; 755037-03-7; BAY 73-4506; BAY-73-4506; BAY73-4506; BAY73-4506 hydrochloride; CHEBI:68647; CHEMBL1946170; UNII-24T2A1DOYB
Indication Colon cancer [ICD11: 2B90] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 482.8 Topological Polar Surface Area 92.4
Heavy Atom Count 33 Rotatable Bond Count 5
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 8
Cross-matching ID
PubChem CID
11167602
PubChem SID
16247148 ; 23360295 ; 42222352 ; 75430857 ; 99437016 ; 123055398 ; 124757057 ; 124772081 ; 125163861 ; 126731249 ; 131480720 ; 135261819 ; 135626856 ; 135727382 ; 136367351 ; 136368060 ; 136920288 ; 136937804 ; 136967459 ; 137245314 ; 137275982 ; 142611634 ; 144115687 ; 152090526 ; 152258021 ; 152258178 ; 152344131 ; 160645781 ; 160647014 ; 162011543 ; 162037486 ; 163698233 ; 164041884 ; 164764796 ; 172087026 ; 172093559 ; 174530361 ; 175267155 ; 175427139 ; 178102514 ; 186014501 ; 188899566 ; 198992717 ; 223381220 ; 223498454 ; 223565986 ; 223680722 ; 223704854 ; 223925935 ; 226756197
ChEBI ID
ChEBI:68647
CAS Number
755037-03-7
TTD Drug ID
D09GDD
Formula
C21H15ClF4N4O3
Canonical SMILES
CNC(=O)C1=NC=CC(=C1)OC2=CC(=C(C=C2)NC(=O)NC3=CC(=C(C=C3)Cl)C(F)(F)F)F
InChI
1S/C21H15ClF4N4O3/c1-27-19(31)18-10-13(6-7-28-18)33-12-3-5-17(16(23)9-12)30-20(32)29-11-2-4-15(22)14(8-11)21(24,25)26/h2-10H,1H3,(H,27,31)(H2,29,30,32)
InChIKey
FNHKPVJBJVTLMP-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
Regorafenib M2 DM016155
53491674
Oxidation - N-oxidation 1 [5] , [2]
Regorafenib M3 DM017903 N. A. Oxidation - Hydroxylation 1 [2]
Regorafenib M7 DM016719
145996739
Conjugation - Glucuronidation 1 [2]
Regorafenib M1 DM016839
156613570
Multi-steps Reaction - N-oxidation; methylhydroxylation 2 [2]
Regorafenib M1 DM016839
156613570
Oxidation - Methylhydroxylation 2 [2]
Regorafenib M4 DM016153
53491672
Oxidation - N-demethylation 2 [2]
Regorafenib M5 DM016154
53491673
Oxidation - N-demethylation 2 [5] , [2]
Regorafenib M6 DM016130
49842244
Oxidation - Oxidation 2 [2]
Regorafenib M8 DM016850
157010680
Conjugation - Glucuronidation 2 [2]
Regorafenib M5 DM016154
53491673
Oxidation - N-demethylation 3 [2]
Regorafenib M5 DM016154
53491673
Oxidation - Demethylation 3 [2]
Regorafenib M6 DM016130
49842244
Oxidation - Oxidation 3 [2]
⏷ Show the Full List of 12  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009514 Regorafenib Regorafenib M2 Oxidation - N-oxidation CYP3A4 [5], [2]
MR009519 Regorafenib Regorafenib M3 Oxidation - Hydroxylation CYP3A4 ... [2]
MR009524 Regorafenib Regorafenib M7 Conjugation - Glucuronidation UGT1A9 [2]
MR009515 Regorafenib M2 Regorafenib M1 Oxidation - Methylhydroxylation CYP3A4 [2]
MR009517 Regorafenib M2 Regorafenib M5 Oxidation - N-demethylation Unclear [5], [2]
MR009518 Regorafenib M2 Regorafenib M8 Conjugation - Glucuronidation UGT1A9 [2]
MR009520 Regorafenib M3 Regorafenib M1 Multi-steps Reaction - N-oxidation; methylhydroxylation Unclear [2]
MR009521 Regorafenib M3 Regorafenib M4 Oxidation - N-demethylation ADH [2]
MR009523 Regorafenib M3 Regorafenib M6 Oxidation - Oxidation Unclear [2]
MR009516 Regorafenib M1 Regorafenib M5 Oxidation - Demethylation Unclear [2]
MR009522 Regorafenib M4 Regorafenib M6 Oxidation - Oxidation Unclear [2]
⏷ 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 2J2 (CYP2J2) DME0031 Homo sapiens
CP2J2_HUMAN
1.14.14.24
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[3]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
S-(hydroxymethyl)glutathione dehydrogenase (adh) DME1249 Vibrio cholerae
A0A0A7DS01_VIBCL
1.1.1.284
[2]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[4]
⏷ Show the Full List of 6  DME(s)
References
1 Regorafenib was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Mass balance, metabolic disposition, and pharmacokinetics of a single oral dose of regorafenib in healthy human subjects
3 FDA Label of Regorafenib. The 2020 official website of the U.S. Food and Drug Administration.
4 Method development and validation for simultaneous determination of six tyrosine kinase inhibitors and two active metabolites in human plasma/serum using UPLC-MS/MS for therapeutic drug monitoring
5 Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS

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