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

General Information of Drug (ID: DR0890)
Drug Name
Isotretinoin
Synonyms
Isotretinoin; Isotretinoin (USP); Isotretinoine; Isotretinoine [INN-French]; Isotretinoino [INN-Spanish]; Isotretinoinum; Isotretinoinum [INN-Latin]; Isotrex; Neovitamin A acid; RETINOIC ACID, 13-cis-; Ro-4-3780; Roaccutan; Roaccutane; Roacutan; Amnesteem; CIP-Isotretinoin; Claravis; ISOTRETINON; Sotret; Teriosal; isotretinoino; (13cis)-retinoic acid; 13-RA; 13-cis RA; 13-cis retinoic acid; 13-cis-Retinoic acid; 13-cis-Vitamin A acid; 4759-48-2; Absorica; Accutane; Accutane (TN); CCRIS 4286; EINECS 225-296-0; HSDB 3929; UNII-EH28UP18IF
Indication Acne vulgaris [ICD11: ED80] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 300.4 Topological Polar Surface Area 37.3
Heavy Atom Count 22 Rotatable Bond Count 5
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 2
Cross-matching ID
PubChem CID
5282379
PubChem SID
9270 ; 821174 ; 3719647 ; 7847414 ; 7979663 ; 8617030 ; 10321605 ; 12013352 ; 14751738 ; 17405637 ; 24278676 ; 24702084 ; 26612253 ; 26747659 ; 26747660 ; 26747661 ; 26753641 ; 26753642 ; 26753643 ; 26753644 ; 39315833 ; 46508729 ; 47193696 ; 47217015 ; 47217016 ; 47440502 ; 47515558 ; 47515559 ; 47515560 ; 47589204 ; 47736730 ; 47885626 ; 48035372 ; 48416136 ; 49698407 ; 50044403 ; 50106981 ; 50106982 ; 53778187 ; 53788737 ; 56312436 ; 56312437 ; 56312464 ; 56313471 ; 56313644 ; 56352887 ; 57288466 ; 57288699 ; 57358641 ; 75174296
ChEBI ID
ChEBI:6067
CAS Number
4759-48-2
TTD Drug ID
D00DKK
Formula
C20H28O2
Canonical SMILES
CC1=C(C(CCC1)(C)C)C=CC(=CC=CC(=CC(=O)O)C)C
InChI
1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14-
InChIKey
SHGAZHPCJJPHSC-XFYACQKRSA-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
4-hydroxy-13-cis-retinoic acid DM001024
102461799
Oxidation - 4-Hydroxylation 1 [4]
Isotretinoin glucuronide DM001025
6506195
Conjugation - Glucuronidation 1 [5]
Retinoic acid DM001016
444795
Unclear 1 [5] , [6] , [4] , [3]
13-cis-4-Oxoretinoic acid DM001019
6437087
Oxidation - Oxidation 2 [7]
16-hydroxyisotretinoin DM001020
122173819
Oxidation - 16-Hydroxylation 2 [5]
18-hydroxyisotretinoin DM001022 N. A. Oxidation - 18-Hydroxylation 2 [5]
4-hydroxyretinoic acid DM002374
6438629
Oxidation - 4-Hydroxylation 2 [7]
16-hydroxyisotretinoin glucuronide DM001021 N. A. Conjugation - Glucuronidation 3 [5]
18-hydroxyisotretinoin glucuronide DM001023 N. A. Conjugation - Glucuronidation 3 [5]
4-Oxoretinoic acid DM002377
6437063
Unclear 3 [7]
4-Oxoretinoic acid DM002377
6437063
Oxidation - Oxidation 3 [7]
13-cis-4-Oxoretinoic acid DM001019
6437087
Other reaction - Trans-Cis Isomerization 4 [7]
⏷ 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
MR001261 Isotretinoin All-trans-retinoic acid Unclear CYP3A4 [5], [6], [4], [3]
MR001262 Isotretinoin 4-hydroxy-13-cis-retinoic acid Oxidation - 4-Hydroxylation CYP3A4 [4]
MR001263 Isotretinoin Isotretinoin glucuronide Conjugation - Glucuronidation Unclear [5]
MR001258 4-hydroxy-13-cis-retinoic acid 4-oxo-13-cis-retinoic acid Oxidation - Oxidation Unclear [7]
MR001252 All-trans-retinoic acid 16-hydroxyisotretinoin Oxidation - 16-Hydroxylation Unclear [5]
MR001253 All-trans-retinoic acid 18-hydroxyisotretinoin Oxidation - 18-Hydroxylation Unclear [5]
MR001254 All-trans-retinoic acid 4-hydroxyretinoic acid Oxidation - 4-Hydroxylation Unclear [7]
MR001256 16-hydroxyisotretinoin 16-hydroxyisotretinoin glucuronide Conjugation - Glucuronidation Unclear [5]
MR001257 18-hydroxyisotretinoin 18-hydroxyisotretinoin glucuronide Conjugation - Glucuronidation Unclear [5]
MR001259 4-hydroxyretinoic acid 4-Oxoretinoic acid Oxidation - Oxidation Unclear [7]
MR001255 4-oxo-13-cis-retinoic acid 4-Oxoretinoic acid Unclear Unclear [7]
MR001260 4-Oxoretinoic acid 4-oxo-13-cis-retinoic acid Other reaction - Trans-Cis Isomerization Unclear [7]
⏷ 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 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_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 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
[2]
References
1 Tretinoin was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Human cytochrome P450s involved in the metabolism of 9-cis- and 13-cis-retinoic acids
3 The effect of isotretinoin on the pharmacokinetics and pharmacodynamics of ethinyl estradiol and norethindrone. Clin Pharmacol Ther. 2004 May;75(5):464-75.
4 The use of isotretinoin in acne Dermatoendocrinol. 2009 May;1(3):162-9. doi: 10.4161/derm.1.3.9364.
5 Human biliary metabolites of isotretinoin: identification, quantification, synthesis, and biological activity Xenobiotica. 1990 Feb;20(2):193-207. doi: 10.3109/00498259009047155.
6 Isotretinoin and its Metabolites Alter mRNA of Multiple Enzyme and Transporter Genes In Vitro, but Downregulation of Organic Anion Transporting Polypeptide Does Not Translate to the Clinic Drug Metab Dispos. 2022 Jul;50(7):1042-1052. doi: 10.1124/dmd.122.000882.
7 DrugBank(Pharmacology-Metabolism)Isotretinoin

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