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

General Information of Drug (ID: DR3420)
Drug Name
Selumetinib
Synonyms
Selumetinib; AZD-6244; ARRY142886; AZD6244; ARRY142886; AZD 6244; AZD-6244; 6UH91I579U; ARRY 142886; ARRY-142886; AZD6244 (Selumetinib); AZD6244(Selumetinib); CHEBI:90227; CHEMBL1614701; MEK inhibitors; Selumetinib (AZD6244); UNII-6UH91I579U
Indication Neurofibromatosis [ICD11: LD2D] Approved [1]
Middle East Respiratory Syndrome (MERS) [ICD11: ICD11: 1D64] Investigative [2]
Severe acute respiratory syndrome (SARS) [ICD11: ICD11: 1D65] Investigative [3]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 457.7 Topological Polar Surface Area 88.4
Heavy Atom Count 27 Rotatable Bond Count 6
Hydrogen Bond Donor Count 3 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
10127622
ChEBI ID
CHEBI:90227
CAS Number
606143-52-6
TTD Drug ID
D0T5DP
Formula
C17H15BrClFN4O3
Canonical SMILES
CN1C=NC2=C1C=C(C(=C2F)NC3=C(C=C(C=C3)Br)Cl)C(=O)NOCCO
InChI
InChI=1S/C17H15BrClFN4O3/c1-24-8-21-16-13(24)7-10(17(26)23-27-5-4-25)15(14(16)20)22-12-3-2-9(18)6-11(12)19/h2-3,6-8,22,25H,4-5H2,1H3,(H,23,26)
InChIKey
CYOHGALHFOKKQC-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
Selumetinib M14 (AZ12791138) DM005193
155804660
Unclear 1 [5]
Selumetinib M15 (AZ13326637) DM005201
16092137
Hydrolysis - Amide hydrolysis 1 [5]
Selumetinib M4 (glucuronidated selumetinib) DM005202 N. A. Conjugation - Glucuronidation 1 [5]
Selumetinib M7 (glucuronidated selumetinib) DM005203 N. A. Conjugation - Glucuronidation 1 [5]
Selumetinib M8 (N-desmethyl selumetinib) DM005189 N. A. Oxidation - N-demethylation 1 [5]
Selumetinib M11 (N-demethylated carboxylic acid selumetinib metabolite) DM005200 N. A. Oxidation - Oxidationn 2 [5]
Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) DM005190
155491127
Other reaction - Elimination 2 [5]
Selumetinib M15 (AZ13326637) DM005201
16092137
Hydrolysis - Amide hydrolysis 2 [5]
Selumetinib M2 (amide glucuronide selumetinib metabolite) DM005194 N. A. Conjugation - Glucuronidation 2 [5]
Selumetinib M3 (glucuronidated N-desmethyl selumetinib) DM005199 N. A. Conjugation - Glucuronidation 2 [5]
Selumetinib M5 (glucuronidated N-desmethyl selumetinib) DM005198 N. A. Conjugation - Glucuronidation 2 [5]
Selumetinib M1 selumetinib metabolite DM005192 N. A. Oxidation - Oxidationn 3 [5]
Selumetinib M10 selumetinib metabolite DM005191 N. A. Oxidation - Oxidationn 3 [5]
Selumetinib M13 (Primary amide, N-demethylated, mono-oxidized selumetinib metabolite) DM005196 N. A. Oxidation - Oxidationn 3 [5]
Selumetinib M6 selumetinib metabolite DM005195 N. A. Oxidation - Oxidationn 3 [5]
Selumetinib M9 (ribose conjugated selumetinib metabolite) DM005197 N. A. Conjugation - Ribose conjugation 3 [5]
Selumetinib M1 selumetinib metabolite DM005192 N. A. Oxidation - Oxidationn 4 [5]
⏷ Show the Full List of 17  DM(s)
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR005610 Selumetinib Selumetinib M8 (N-desmethyl selumetinib) Oxidation - N-demethylation Unclear [5]
MR005614 Selumetinib Selumetinib M14 (AZ12791138) Unclear Unclear [5]
MR005625 Selumetinib Selumetinib M15 (AZ13326637) Hydrolysis - Amide hydrolysis Unclear [5]
MR005626 Selumetinib Selumetinib M4 (glucuronidated selumetinib) Conjugation - Glucuronidation Unclear [5]
MR005627 Selumetinib Selumetinib M7 (glucuronidated selumetinib) Conjugation - Glucuronidation Unclear [5]
MR005615 Selumetinib M14 (AZ12791138) Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) Other reaction - Elimination Unclear [5]
MR005616 Selumetinib M14 (AZ12791138) Selumetinib M2 (amide glucuronide selumetinib metabolite) Conjugation - Glucuronidation Unclear [5]
MR005624 Selumetinib M14 (AZ12791138) Selumetinib M15 (AZ13326637) Hydrolysis - Amide hydrolysis Unclear [5]
MR005611 Selumetinib M8 (N-desmethyl selumetinib) Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) Other reaction - Elimination Unclear [5]
MR005621 Selumetinib M8 (N-desmethyl selumetinib) Selumetinib M5 (glucuronidated N-desmethyl selumetinib) Conjugation - Glucuronidation Unclear [5]
MR005622 Selumetinib M8 (N-desmethyl selumetinib) Selumetinib M3 (glucuronidated N-desmethyl selumetinib) Conjugation - Glucuronidation Unclear [5]
MR005623 Selumetinib M8 (N-desmethyl selumetinib) Selumetinib M11 (N-demethylated carboxylic acid selumetinib metabolite) Oxidation - Oxidationn Unclear [5]
MR005612 Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) Selumetinib M10 selumetinib metabolite Oxidation - Oxidationn Unclear [5]
MR005619 Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) Selumetinib M13 (Primary amide, N-demethylated, mono-oxidized selumetinib metabolite) Oxidation - Oxidationn Unclear [5]
MR005620 Selumetinib M12 (Primary amide, N-demethylated selumetinib metabolite) Selumetinib M9 (ribose conjugated selumetinib metabolite) Conjugation - Ribose conjugation Unclear [5]
MR005617 Selumetinib M2 (amide glucuronide selumetinib metabolite) Selumetinib M1 selumetinib metabolite Oxidation - Oxidationn Unclear [5]
MR005618 Selumetinib M2 (amide glucuronide selumetinib metabolite) Selumetinib M6 selumetinib metabolite Oxidation - Oxidationn Unclear [5]
MR005613 Selumetinib M10 selumetinib metabolite Selumetinib M1 selumetinib metabolite Oxidation - Oxidationn Unclear [5]
⏷ Show the Full List of 18 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
[4] , [5]
Cytochrome P450 2A6 (CYP2A6) DME0005 Homo sapiens
CP2A6_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] , [5]
Cytochrome P450 2E1 (CYP2E1) DME0013 Homo sapiens
CP2E1_HUMAN
1.14.14.1
[4]
Cytochrome P450 3A4 (CYP3A4) DME0001 Homo sapiens
CP3A4_HUMAN
1.14.14.55
[4]
Cytochrome P450 3A5 (CYP3A5) DME0012 Homo sapiens
CP3A5_HUMAN
1.14.14.1
[4]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[4] , [5]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[4]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[4]
⏷ Show the Full List of 10  DME(s)
References
1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
3 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
4 Physiologically Based Pharmacokinetic Modeling for Selumetinib to Evaluate Drug-Drug Interactions and Pediatric Dose Regimens
5 Metabolism, Excretion, and Pharmacokinetics of Selumetinib, an MEK1/2 inhibitor, in Healthy Adult Male Subjects

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