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

General Information of Drug (ID: DR0121)
Drug Name
Apalutamide
Synonyms
Apalutamide [INN]; Erleada; JNJ-56021927; apalutamide; ARN 509; ARN-509; ARN509; 4-(7-(6-CYANO-5-(TRIFLUOROMETHYL)PYRIDIN-3-YL)-8-OXO-6-THIOXO-5,7-DIAZASPIRO[3.4]OCTAN-5-YL)-2-FLUORO-N-METHYLBENZAMIDE; 4-(7-(6-cyano-5-(trifluoroMethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspirooctan-5-yl)-2-fluoro-N-MethylbenzaMide; 4-[7-[6-cyano-5-(trifluoromethyl)pyridin-3-yl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-N-methylbenzamide; 4T36H88UA7; 956104-40-8; AR509; UNII-4T36H88UA7
Indication Acute myeloid leukaemia [ICD11: 2A60] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 477.4 Topological Polar Surface Area 121
Heavy Atom Count 33 Rotatable Bond Count 3
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 9
Cross-matching ID
PubChem CID
24872560
PubChem SID
50127665 ; 57161266 ; 152159708 ; 152258720 ; 160647563 ; 162012009 ; 162108672 ; 162205209 ; 164045137 ; 165245619 ; 170501902 ; 174007290 ; 174531399 ; 185990492 ; 189024879 ; 198977777 ; 223388726 ; 223471410 ; 223705154 ; 224466409 ; 227174897 ; 242586422 ; 251962968 ; 252110202 ; 252160623 ; 252214876 ; 252455417
CAS Number
956104-40-8
TTD Drug ID
D0S7LG
Formula
C21H15F4N5O2S
Canonical SMILES
CNC(=O)C1=C(C=C(C=C1)N2C(=S)N(C(=O)C23CCC3)C4=CC(=C(N=C4)C#N)C(F)(F)F)F
InChI
1S/C21H15F4N5O2S/c1-27-17(31)13-4-3-11(8-15(13)22)30-19(33)29(18(32)20(30)5-2-6-20)12-7-14(21(23,24)25)16(9-26)28-10-12/h3-4,7-8,10H,2,5-6H2,1H3,(H,27,31)
InChIKey
HJBWBFZLDZWPHF-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
Apalutamide metabolite M10 DM001380
156028066
Conjugation - Cysteine-Glycine Condensation 1 [3]
Apalutamide metabolite M13 DM001388
155929107
Hydrolysis - Nitrile Hydrolysis 1 [3]
Apalutamide metabolite M19 DM001385
90285493
Unclear 1 [3]
Apalutamide metabolite M2 DM001393
67373212
Oxidation - Oxidation; Desulfuration 1 [3]
Apalutamide metabolite M4 DM001382
8668348
Hydrolysis - Amide Hydrolysis 1 [3]
Apalutamide metabolite M8 DM001390 N. A. Oxidation - Oxidation 1 [3]
Apalutamide metabolite M9 DM001381
156596400
Unclear 1 [3]
N-desmethyl apalutamide DM001376
86683490
Oxidation - N-Demethylation 1 [3]
Apalutamide metabolite M11 DM001391 N. A. Unclear 2 [3]
Apalutamide metabolite M12 DM001377
165412047
Unclear 2 [3]
Apalutamide metabolite M14 DM001378
165412051
Unclear 2 [3]
Apalutamide metabolite M15 DM001389
156596557
Unclear 2 [3]
Apalutamide metabolite M18 DM001384
156613864
Unclear 2 [3]
Apalutamide metabolite M20 DM001386 N. A. Unclear 2 [3]
Apalutamide metabolite M21 DM001392
155929078
Unclear 2 [3]
Apalutamide metabolite M4 DM001382
8668348
Unclear 2 [3]
Apalutamide metabolite M5 DM001383 N. A. Unclear 2 [3]
Apalutamide metabolite M9 DM001381
156596400
Conjugation - Cysteine Condensation 2 [3]
Apalutamide metabolite M14 DM001378
165412051
Unclear 3 [3]
Apalutamide metabolite M17 DM001379
165412048
Unclear 3 [3]
Apalutamide metabolite M18 DM001384
156613864
Unclear 3 [3]
Apalutamide metabolite M22 DM001387
156613997
Unclear 3 [3]
Apalutamide metabolite M17 DM001379
165412048
Unclear 4 [3]
⏷ Show the Full List of 23  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR003361 Apalutamide N-desmethyl apalutamide Oxidation - N-Demethylation CYP2C8 ... [3]
MR003362 Apalutamide Apalutamide metabolite M10 Conjugation - Cysteine-Glycine Condensation Unclear [3]
MR003363 Apalutamide Apalutamide metabolite M9 Unclear Unclear [3]
MR003364 Apalutamide Apalutamide metabolite M4 Hydrolysis - Amide Hydrolysis Unclear [3]
MR003365 Apalutamide Apalutamide metabolite M19 Unclear Unclear [3]
MR003366 Apalutamide Apalutamide metabolite M13 Hydrolysis - Nitrile Hydrolysis Unclear [3]
MR003367 Apalutamide Apalutamide metabolite M8 Oxidation - Oxidation Unclear [3]
MR003368 Apalutamide Apalutamide metabolite M2 Oxidation - Oxidation; Desulfuration Unclear [3]
MR003349 Apalutamide metabolite M10 Apalutamide metabolite M12 Unclear Unclear [3]
MR003350 Apalutamide metabolite M10 Apalutamide metabolite M9 Conjugation - Cysteine Condensation Unclear [3]
MR003358 Apalutamide metabolite M13 Apalutamide metabolite M15 Unclear Unclear [3]
MR003355 Apalutamide metabolite M19 Apalutamide metabolite M20 Unclear Unclear [3]
MR003356 Apalutamide metabolite M19 Apalutamide metabolite M21 Unclear Unclear [3]
MR003353 Apalutamide metabolite M4 Apalutamide metabolite M18 Unclear Unclear [3]
MR003360 Apalutamide metabolite M8 Apalutamide metabolite M11 Unclear Unclear [3]
MR003343 N-desmethyl apalutamide Apalutamide metabolite M12 Unclear Unclear [3]
MR003344 N-desmethyl apalutamide Apalutamide metabolite M14 Unclear Unclear [3]
MR003345 N-desmethyl apalutamide Apalutamide metabolite M4 Unclear Unclear [3]
MR003346 N-desmethyl apalutamide Apalutamide metabolite M5 Unclear Unclear [3]
MR003347 Apalutamide metabolite M12 Apalutamide metabolite M14 Unclear Unclear [3]
MR003359 Apalutamide metabolite M15 Apalutamide metabolite M18 Unclear Unclear [3]
MR003357 Apalutamide metabolite M20 Apalutamide metabolite M22 Unclear Unclear [3]
MR003352 Apalutamide metabolite M4 Apalutamide metabolite M17 Unclear Unclear [3]
MR003354 Apalutamide metabolite M5 Apalutamide metabolite M18 Unclear Unclear [3]
MR003351 Apalutamide metabolite M9 Apalutamide metabolite M14 Unclear Unclear [3]
MR003348 Apalutamide metabolite M14 Apalutamide metabolite M17 Unclear Unclear [3]
⏷ Show the Full List of 26 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
[2]
References
1 Omeprazole was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Apalutamide: first global approval. Drugs. 2018 Apr;78(6):699-705.
3 Apalutamide Absorption, Metabolism, and Excretion in Healthy Men, and Enzyme Reaction in Human Hepatocytes Drug Metab Dispos. 2019 May;47(5):453-464. doi: 10.1124/dmd.118.084517.

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