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

General Information of Drug (ID: DR1634)
Drug Name
Tretinoin
Synonyms
Aknefug; Aknoten; All-trans Retinoic Acid; Alltrans-retinoic acid; Atralin; Cordes vas; Dermairol; Effederm; Epi-aberel; Eudyna; Renova; Retin-A; Retin-A Micro; Retinoic acid; Retinoic acid, all-trans-; Retionic acid; TRETINON; Tretin M; Vesanoid; Vitamin A acid; Vitamin A acid, all-trans-; Vitamin A1 acid, all-trans-; all-trans-Retinoic acid; all-trans-Tretinoin; all-trans-Vitamin A acid; all-trans-Vitamin A1 acid; beta-Ra; beta-Retinoic acid; trans-Retinoic acid; tretinoin; 302-79-4; ATRA; Aberel; Airol; all-(E)-Retinoic acid
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
444795
PubChem SID
4038 ; 416403 ; 596063 ; 830710 ; 838467 ; 841067 ; 855632 ; 3138737 ; 7847162 ; 7890244 ; 7980826 ; 8143163 ; 8149916 ; 10299585 ; 10321438 ; 11528311 ; 12014646 ; 14825303 ; 14849563 ; 17405617 ; 24278674 ; 24702082 ; 26612256 ; 26680099 ; 26703748 ; 26716947 ; 26746936 ; 26746937 ; 26759442 ; 29214999 ; 31294611 ; 36887697 ; 46392576 ; 46487923 ; 47216527 ; 47959456 ; 47959457 ; 48110185 ; 48110186 ; 48184725 ; 48184726 ; 48184727 ; 48184728 ; 48258941 ; 48414424 ; 48483920 ; 49698408 ; 50103969 ; 50103970 ; 50126361
ChEBI ID
ChEBI:15367
CAS Number
302-79-4
TTD Drug ID
D02DGU
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-YCNIQYBTSA-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
13-cis-retinoic acid DM007065
5282379
Other reaction - Isomerization 1 [2] , [6]
3,4-Didehydroretinoic acid DM015297
447276
Oxidation - Oxidation 1 [7]
4-hydroxyretinoic acid DM002374
6438629
Oxidation - 4-hydroxylation 1 [5] , [2]
5,6-epoxy-RA DM002376
5363137
Oxidation - Ring epoxidation 1 [6] , [6] , [5]
9-cis-retinoic acid DM007066
449171
Other reaction - Isomerization 1 [2] , [6]
All-trans-18-Hydroxyretinoic acid DM002375
6506224
Oxidation - Hydroxylation 1 [5] , [6] , [2]
Retinotaurine DM015497
6439605
Oxidation - Oxidation 1 [7]
Retinoyl glucuronide DM002378
5281877
Conjugation - Glucuronidation 1 [7]
13-cis-4-Oxoretinoic acid DM001019
6437087
Oxidation - Oxidation 2 [2]
13-cis-Retinoyl-beta-glucuronide DM015500
6439753
Conjugation - Glucuronidation 2 [7] , [8]
4-Oxoretinoic acid DM002377
6437063
Oxidation - Oxidation 2 [5] , [6]
9-cis-4-Oxoretinoic acid DM000857
9972939
Oxidation - Oxidation 2 [2]
Rac-5,6-Epoxy-retinoyl-beta-D-glucuronide DM016587
131769835
Conjugation - Glucuronidation 2 [7]
4-Oxoretinoic acid glucuronide DM017937 N. A. Conjugation - Glucuronidation 3 [7]
⏷ Show the Full List of 14  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR009626 Tretinoin 4-Hydroxyretinoic acid Oxidation - 4-hydroxylation CYP2C8 ... [5], [2]
MR009629 Tretinoin 5,6-epoxy-RA Oxidation - Ring epoxidation CYP2C8 ... [6], [6], [5]
MR009631 Tretinoin 13-cis RA Other reaction - Isomerization CYP2C8 ... [2], [6]
MR009634 Tretinoin 9-cis RA Other reaction - Isomerization CYP2C8 ... [2], [6]
MR009636 Tretinoin 18-OH-RA Oxidation - Hydroxylation CYP2C8 ... [5], [6], [2]
MR009637 Tretinoin 3,4-Didehydroretinoic acid Oxidation - Oxidation Unclear [7]
MR009638 Tretinoin Retinotaurine Oxidation - Oxidation Unclear [7]
MR009639 Tretinoin Retinoyl beta-glucuronide Conjugation - Glucuronidation Unclear [7]
MR009632 13-cis RA 13-cis-Retinoyl-beta-glucuronide Conjugation - Glucuronidation Unclear [7], [8]
MR009633 13-cis RA 13-cis-4-Oxoretinoic acid Oxidation - Oxidation Unclear [2]
MR009627 4-Hydroxyretinoic acid 4-Oxoretinoic acid Oxidation - Oxidation CYP3A7 ... [5], [6]
MR009630 5,6-epoxy-RA Rac-5,6-Epoxy-retinoyl-beta-D-glucuronide Conjugation - Glucuronidation Unclear [7]
MR009635 9-cis RA 9-cis-4-Oxoretinoic acid Oxidation - Oxidation Unclear [2]
MR009628 4-Oxoretinoic acid 4-Oxoretinoic acid glucuronide Conjugation - Glucuronidation Unclear [7]
⏷ Show the Full List of 14 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
Cytochrome P450 1A1 (CYP1A1) DME0006 Homo sapiens
CP1A1_HUMAN
1.14.14.1
[2]
Cytochrome P450 26C1 (CYP26C1) DME0600 Homo sapiens
CP26C_HUMAN
1.14.11.1
[3]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_HUMAN
1.14.14.1
[4]
Cytochrome P450 2B6 (CYP2B6) DME0020 Homo sapiens
CP2B6_HUMAN
1.14.14.1
[4]
Cytochrome P450 2C18 (CYP2C18) DME0017 Homo sapiens
CP2CI_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C8 (CYP2C8) DME0018 Homo sapiens
CP2C8_HUMAN
1.14.14.1
[5]
Cytochrome P450 2C9 (CYP2C9) DME0019 Homo sapiens
CP2C9_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[5]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[5]
Cytochrome P450 3A7 (CYP3A7) DME0015 Homo sapiens
CP3A7_HUMAN
1.14.14.1
[5]
Lauric acid omega-hydroxylase (CYP4A11) DME0029 Homo sapiens
CP4AB_HUMAN
1.14.15.3
[5]
Retinoic acid 4-hydroxylase 26A1 (CYP26A1) DME0227 Homo sapiens
CP26A_HUMAN
1.14.13.-
[6]
⏷ Show the Full List of 12  DME(s)
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 CYP26C1 is a hydroxylase of multiple active retinoids and interacts with cellular retinoic acid binding proteins. Mol Pharmacol. 2018 May;93(5):489-503.
4 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
5 Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol. 2000 Dec;58(6):1341-8.
6 Retinoic acid metabolism and mechanism of action: a review
7 Clinical pharmacokinetics of tretinoin
8 13-cis retinoyl-beta-glucuronide in lacrimal gland fluid of rabbits treated with 13-cis retinoic acid

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