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

General Information of Drug (ID: DR1524)
Drug Name
Tacrolimus
Synonyms
Tacarolimus; Tacrolimus (anhydrous); Tacrolimus [USAN]; Tacrolimus anhydrous; Tsukubaenolide; Y5L2157C4J; tacrolimus; Advagraf; Anhydrous Tacrolimus; Astagraf XL; Avagraf; Envarsus; Envarsus XR; Fujimycin; Graceptor; L 679934; LCP-Tacro; Modigraf; Prograf; Prograf (TN); Prograft; Protopic; Protopy; tacrolimus (fk506); (-)-FK 506; 104987-11-3; 109581-93-3; 8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN; CCRIS 7124; CHEBI:61049; CHEMBL269732; FK 506; FK5; FK506; FR 900506; FR-900506; FR900506; Fk-506; K506; MFCD11045918; NCGC00163470-03; UNII-Y5L2157C4J
Indication Ulcerative colitis [ICD11: DD71] Approved []
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 804 Topological Polar Surface Area 178
Heavy Atom Count 57 Rotatable Bond Count 7
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 12
Cross-matching ID
PubChem CID
445643
PubChem SID
4572 ; 832905 ; 842004 ; 7887491 ; 7980719 ; 8150098 ; 10299743 ; 12013904 ; 14815954 ; 14889261 ; 24841759 ; 26703416 ; 26705532 ; 26705535 ; 26713140 ; 26715494 ; 26756858 ; 29216422 ; 36888289 ; 46506004 ; 47574395 ; 48020022 ; 50111459 ; 50111460 ; 53788265 ; 57404698 ; 74380484 ; 76558282 ; 85788970 ; 91011629 ; 92308089 ; 92310166 ; 92711966 ; 96025241 ; 99301078 ; 99302128 ; 99436940 ; 103164549 ; 103939344 ; 104178757 ; 104222107 ; 104634734 ; 109693101 ; 118048657 ; 119525750 ; 124757870 ; 124766122 ; 124892446 ; 124892447 ; 124892448
ChEBI ID
CHEBI:61049
CAS Number
104987-11-3
TTD Drug ID
D06OMK
Formula
C44H69NO12
Canonical SMILES
CC1CC(C2C(CC(C(O2)(C(=O)C(=O)N3CCCCC3C(=O)OC(C(C(CC(=O)C(C=C(C1)C)CC=C)O)C)C(=CC4CCC(C(C4)OC)O)C)O)C)OC)OC
InChI
1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1
InChIKey
QJJXYPPXXYFBGM-LFZNUXCKSA-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
12-hydroxy tacrolimus DM000426 N. A. Oxidation - Deamination 1 [6]
13-demethyl tacrolimus DM000421
131769926
Oxidation - Deamination 1 [6]
13-O-Desmethyltacrolimus DM000429
154699847
Oxidation - Deamination 1 [6]
15,31-didemethyl tacrolimus DM000427 N. A. Oxidation - Deamination 1 [6]
15-demethyl tacrolimus DM000425 N. A. Oxidation - Deamination 1 [6]
15-O-Desmethyltacrolimus DM000430
101656646
Oxidation - Deamination 1 [6]
31-demethyl tacrolimus DM000424 N. A. Oxidation - Deamination 1 [6]
31-O-Demethyltacrolimus DM000428
131770014
Oxidation - Deamination 1 [6]
13,15-didemethyl tacrolimus DM000423 N. A. Oxidation - Deamination 2 [6]
13,31-didemethyl tacrolimus DM000422 N. A. Oxidation - Deamination 2 [6]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR002319 Tacrolimus 13-demethyl tacrolimus Oxidation - Deamination CYP3A4 [6]
MR002320 Tacrolimus 31-demethyl tacrolimus Oxidation - Deamination CYP3A4 [6]
MR002321 Tacrolimus 15-demethyl tacrolimus Oxidation - Deamination CYP3A4 [6]
MR002322 Tacrolimus 12-hydroxy tacrolimus Oxidation - Deamination CYP3A4 [6]
MR002323 Tacrolimus 15,31-didemethyl tacrolimus Oxidation - Deamination CYP3A4 [6]
MR002324 Tacrolimus 31-O-Demethyltacrolimus Oxidation - Deamination CYP3A4 ... [6]
MR002325 Tacrolimus 13-O-Desmethyltacrolimus Oxidation - Deamination CYP3A4 ... [6]
MR002326 Tacrolimus 15-O-Desmethyltacrolimus Oxidation - Deamination CYP3A4 ... [6]
MR002317 13-demethyl tacrolimus 13,31-didemethyl tacrolimus Oxidation - Deamination CYP3A5 [6]
MR002318 13-demethyl tacrolimus 13,15-didemethyl tacrolimus Oxidation - Deamination CYP3A5 [6]
⏷ Show the Full List of 10 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
[1]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[2]
NADPH-cytochrome P450 reductase (CPR) DME0076 Homo sapiens
NCPR_HUMAN
1.6.2.4
[3]
Ribosomal 23S RNA methyltransferase Erm (erm) DME1156 Corynebacterium amycolatum
A0A5N1AHF6_CORAY
2.1.1.182
[4]
Ribosomal 23S RNA methyltransferase Erm (erm) DME1238 Corynebacterium jeikeium
A0A381KDL2_CORJE
2.1.1.182
[4]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1254 Bacteroides thetaiotaomicron Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1265 Escherichia coli Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1355 Akkermansia muciniphila Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1357 Alistipes indistinctus Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1366 Bacteroides eggerthii Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1393 Blautia hansenii Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1394 Blautia luti Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1398 Clostridioides difficile Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1402 Clostridium botulinum Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1404 Clostridium sporogenes Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1415 Eggerthella lenta Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1420 Erysipelatoclostridium ramosum Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1431 Holdemanella biformis Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1447 Parabacteroides merdae Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1452 Providencia alcalifaciens Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1456 Roseburia intestinalis Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1458 Ruminococcus gnavus Not Available Not Available [5]
Unclear metabolic mechanism (DME-unclear) DME1470 Victivallis vadensis Not Available Not Available [5]
⏷ Show the Full List of 28  DME(s)
References
1 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
2 Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol. 2007 Aug;21(4):427-35.
3 Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy. Pharmacogenet Genomics. 2017 Sep;27(9):337-346.
4 High frequency of macrolide resistance mechanisms in clinical isolates of Corynebacterium species. Microb Drug Resist. 2010 Dec;16(4):273-7.
5 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.
6 Metabolism of tacrolimus (FK506) and recent topics in clinical pharmacokinetics Drug Metab Pharmacokinet. 2007 Oct;22(5):328-35. doi: 10.2133/dmpk.22.328.

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