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

General Information of Drug (ID: DR0892)
Drug Name
Istradefylline
Synonyms
Istradefylline; Istradefylline (KW-6002); KW 6002; KW-6002; (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methyl-1H-purine-2,6(3H,7H)-dione; (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1H-purine-2,6-dione; (E)-8-(3,4-Dimethoxystyryl)-1,3-diethyl-7-methylxanthine; 155270-99-8; 2GZ0LIK7T4; 8-[(E)-2-(3,4-Dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methyl-purine-2,6 -dione; 8-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione; CHEMBL431770; UNII-2GZ0LIK7T4
Indication Parkinsonism [ICD11: 8A00] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 384.4 Topological Polar Surface Area 76.9
Heavy Atom Count 28 Rotatable Bond Count 6
Hydrogen Bond Donor Count 0 Hydrogen Bond Acceptor Count 5
Cross-matching ID
PubChem CID
5311037
PubChem SID
7978842 ; 11056223 ; 12014869 ; 14878146 ; 39340766 ; 47206484 ; 50027674 ; 50629398 ; 57359333 ; 85210094 ; 92729739 ; 103276933 ; 104061724 ; 114155109 ; 126671671 ; 134338968 ; 134339069 ; 134343014 ; 135175557 ; 135697573 ; 137005694 ; 140175846 ; 144116113 ; 152105687 ; 152159601 ; 152258274 ; 152343827 ; 160647112 ; 162011669 ; 162222240 ; 163408039 ; 163914047 ; 164777218 ; 170466116 ; 172093763 ; 172912718 ; 174527720 ; 175437836 ; 178102242 ; 179150002 ; 185975314 ; 198959942 ; 206245955 ; 208265417 ; 223378751 ; 223435458 ; 223496120 ; 223554827 ; 223660299 ; 223704923
ChEBI ID
CHEBI:134726
CAS Number
155270-99-8
TTD Drug ID
D0F4ZY
Formula
C20H24N4O4
Canonical SMILES
CCN1C2=C(C(=O)N(C1=O)CC)N(C(=N2)C=CC3=CC(=C(C=C3)OC)OC)C
InChI
1S/C20H24N4O4/c1-6-23-18-17(19(25)24(7-2)20(23)26)22(3)16(21-18)11-9-13-8-10-14(27-4)15(12-13)28-5/h8-12H,6-7H2,1-5H3/b11-9+
InChIKey
IQVRBWUUXZMOPW-PKNBQFBNSA-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
1-beta-hydroxy-4'-O-demethyl Istradefylline DM001037 N. A. Unclear 1 [2]
1-beta-hydroxylated Istradefylline DM001038
125300463
Oxidation - Hydroxylation 1 [2]
3',4'-O-didemethyl Istradefylline DM001035 N. A. Unclear 1 [2]
4'-O-monodesmethyl istradefylline DM001032
135665340
Oxidation - O-Demethylation 1 [2] , [3]
Istradefylline M1 glucuronide DM001033 N. A. Conjugation - O-Glucuronidation 2 [2]
Istradefylline M1 sulfate conjugate DM001034 N. A. Conjugation - Sulfation 2 [2]
Istradefylline metabolite M10 DM001036
145722039
Unclear 2 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR001273 Istradefylline 4'-O-monodesmethyl istradefylline Oxidation - O-Demethylation CYP3A4 [2], [3]
MR001274 Istradefylline 3',4'-O-didemethyl Istradefylline Unclear Unclear [2]
MR001275 Istradefylline 1-beta-hydroxy-4'-O-demethyl Istradefylline Unclear Unclear [2]
MR001276 Istradefylline 1-beta-hydroxylated Istradefylline Oxidation - Hydroxylation CYP3A4 ... [2]
MR001272 3',4'-O-didemethyl Istradefylline Istradefylline metabolite M10 Unclear Unclear [2]
MR001270 4'-O-monodesmethyl istradefylline Istradefylline M1 glucuronide Conjugation - O-Glucuronidation Unclear [2]
MR001271 4'-O-monodesmethyl istradefylline Istradefylline M1 sulfate conjugate Conjugation - Sulfation Unclear [2]
⏷ Show the Full List of 7 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A2 (CYP1A2) DME0003 Homo sapiens
CP1A2_HUMAN
1.14.14.1
[2]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[2]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[2]
Cytochrome P450 2D6 (CYP2D6) DME0009 Homo sapiens
CP2D6_HUMAN
1.14.14.1
[2]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[2]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
⏷ Show the Full List of 8  DME(s)
References
1 Istradefylline was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Effects of rifampin on the pharmacokinetics of a single dose of istradefylline in healthy subjects. J Clin Pharmacol. 2018 Feb;58(2):193-201.
3 The effect of CYP3A4 genetic polymorphism and drug interaction on the metabolism of istradefylline Chem Biol Interact. 2022 Oct 1;366:110123. doi: 10.1016/j.cbi.2022.110123.

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