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

General Information of Drug (ID: DR0419)
Drug Name
Darolutamide
Synonyms
Darolutamide; Darolutamide (ODM-201); Nubeqa; ODM-201; ODM201; X05U0N2RCO; 1297538-32-9; 1H-Pyrazole-3-carboxamide, N-[(1S)-2-[3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl]-1-methylethyl]-5-(1-hydroxyethyl)-; BAY-1841788; BAY1841788; N-((S)-1-(3-(3-Chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-(1-hydroxyethyl)-1H-pyrazole-3-carboxamide; N-((S)-1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)-propan-2-yl)-3-(1-hydroxyethyl)-1H-pyrazole-5-carboxamide; UNII-X05U0N2RCO
Indication Prostate cancer [ICD11: 2C82] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 398.8 Topological Polar Surface Area 120
Heavy Atom Count 28 Rotatable Bond Count 6
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
67171867
CAS Number
1297538-32-9
TTD Drug ID
D0DV6D
Formula
C19H19ClN6O2
Canonical SMILES
CC(CN1C=CC(=N1)C2=CC(=C(C=C2)C#N)Cl)NC(=O)C3=NNC(=C3)C(C)O
InChI
1S/C19H19ClN6O2/c1-11(22-19(28)18-8-17(12(2)27)23-24-18)10-26-6-5-16(25-26)13-3-4-14(9-21)15(20)7-13/h3-8,11-12,27H,10H2,1-2H3,(H,22,28)(H,23,24)/t11-,12?/m0/s1
InChIKey
BLIJXOOIHRSQRB-PXYINDEMSA-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
Ketodarolutamide DM001892
52919826
Oxidation - Oxidation 1 [3] , [4] , [5]
Darolutamide metabolite M10 DM001900 N. A. Conjugation - Glucuronidation 2 [6]
Darolutamide metabolite M15a,15b DM001908 N. A. Conjugation - Glucuronidation 2 [6]
Darolutamide metabolite M2 DM001906 N. A. Conjugation - Glucuronidation 2 [6]
Darolutamide metabolite M28 DM001901
70655566
Unclear 2 [6]
Darolutamide metabolite M31 DM001893
155665791
Unclear 2 [6]
Darolutamide metabolite M32 DM001905 N. A. Oxidation - N-Dealkylation 2 [6]
Darolutamide metabolite M33 DM001904 N. A. Oxidation - N-Dealkylation 2 [6]
Darolutamide metabolite M34 DM001902
141333439
Oxidation - N-Dealkylation 2 [6]
Darolutamide metabolite M36 DM001903 N. A. Oxidation - N-Dealkylation 2 [6]
Darolutamide metabolite M7a,7b DM001907 N. A. Conjugation - Glucuronidation 2 [6]
Darolutamide metabolite M26 DM001894
67170102
Unclear 3 [6]
Darolutamide metabolite M30 DM001899 N. A. Reduction - Reduction 3 [6]
Darolutamide metabolite M25 DM001895 N. A. Oxidation - Hydroxylation 4 [6]
Darolutamide metabolite M29 DM001898 N. A. Oxidation - Hydroxylation 4 [6]
Darolutamide metabolite M21 DM001897 N. A. Conjugation - Glucuronidation 5 [6]
Darolutamide metabolite M24 DM001896 N. A. Unclear 5 [6]
Darolutamide metabolite M21 DM001897 N. A. Conjugation - Glucuronidation 6 [6]
⏷ Show the Full List of 18  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR003222 Darolutamide Ketodarolutamide Oxidation - Oxidation UGT1A9 ... [3], [4], [5]
MR003223 Darolutamide Darolutamide metabolite M31 Unclear Unclear [6]
MR003224 Darolutamide Darolutamide metabolite M34 Oxidation - N-Dealkylation Unclear [6]
MR003225 Darolutamide Darolutamide metabolite M36 Oxidation - N-Dealkylation Unclear [6]
MR003226 Darolutamide Darolutamide metabolite M33 Oxidation - N-Dealkylation Unclear [6]
MR003227 Darolutamide Darolutamide metabolite M32 Oxidation - N-Dealkylation Unclear [6]
MR003228 Darolutamide Darolutamide metabolite M2 Conjugation - Glucuronidation Unclear [6]
MR003229 Darolutamide Darolutamide metabolite M7a,7b Conjugation - Glucuronidation Unclear [6]
MR003230 Darolutamide Darolutamide metabolite M15a,15b Conjugation - Glucuronidation Unclear [6]
MR003210 Ketodarolutamide Darolutamide metabolite M31 Unclear Unclear [6]
MR003211 Ketodarolutamide Darolutamide metabolite M10 Conjugation - Glucuronidation Unclear [6]
MR003212 Ketodarolutamide Darolutamide metabolite M28 Unclear Unclear [6]
MR003213 Ketodarolutamide Darolutamide metabolite M34 Oxidation - N-Dealkylation Unclear [6]
MR003214 Ketodarolutamide Darolutamide metabolite M36 Oxidation - N-Dealkylation Unclear [6]
MR003215 Ketodarolutamide Darolutamide metabolite M33 Oxidation - N-Dealkylation Unclear [6]
MR003216 Darolutamide metabolite M31 Darolutamide metabolite M26 Unclear Unclear [6]
MR003217 Darolutamide metabolite M31 Darolutamide metabolite M30 Reduction - Reduction Unclear [6]
MR003218 Darolutamide metabolite M26 Darolutamide metabolite M25 Oxidation - Hydroxylation Unclear [6]
MR003219 Darolutamide metabolite M26 Darolutamide metabolite M29 Oxidation - Hydroxylation Unclear [6]
MR003220 Darolutamide metabolite M25 Darolutamide metabolite M24 Unclear Unclear [6]
MR003221 Darolutamide metabolite M25 Darolutamide metabolite M21 Conjugation - Glucuronidation Unclear [6]
⏷ Show the Full List of 21 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
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 1A8 (UGT1A8) DME0064 Homo sapiens
UD18_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DME0042 Homo sapiens
UD19_HUMAN
2.4.1.17
[2]
UDP-glucuronosyltransferase 2B17 (UGT2B17) DME0066 Homo sapiens
UDB17_HUMAN
2.4.1.17
[2]
⏷ Show the Full List of 6  DME(s)
References
1 Darolutamide was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Drug-drug interaction potential of darolutamide: in vitro and clinical studies. Eur J Drug Metab Pharmacokinet. 2019 Dec;44(6):747-759.
3 Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer Clin Genitourin Cancer. 2018 Oct;16(5):332-340. doi: 10.1016/j.clgc.2018.07.017.
4 Drug-Drug Interaction Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Ipatasertib in Combination with Darolutamide in Patients with Advanced Prostate Cancer. Pharmaceutics. 2022 Oct 1;14(10):2101. doi: 10.3390/pharmaceutics14102101.
5 Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. Clin Pharmacokinet. 2022 Apr;61(4):565-575. doi: 10.1007/s40262-021-01078-y.
6 Metabolism and Mass Balance of the Novel Nonsteroidal Androgen Receptor Inhibitor Darolutamide in Humans Drug Metab Dispos. 2021 Jun;49(6):420-433. doi: 10.1124/dmd.120.000309.

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