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

General Information of Drug (ID: DR0998)
Drug Name
Macitentan
Synonyms
Macitentan; Macitentan (JAN/USAN); Macitentan [USAN:INN]; Opsumit; Opsumit (TN); Actelion-1; SCHEMBL1445625; Z9K9Y9WMVL; ZLA0005; macitentanum; zlchem 5; (non-labelled)Macitentan-d7; 441798-33-0; ACT 064992; ACT-064992; ACT064992; C19H20Br2N6O4S; CHEBI:76607; CHEMBL2103873; DTXSID50196063; EX-A544; GTPL7352; MLS006011174; N-(5-(4-Bromophenyl)-6-(2-((5-bromo-2-pyrimidinyl)oxy)ethoxy)-4-pyrimidinyl)-N'-propylsulfamide; N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide; UNII-Z9K9Y9WMVL
Indication Pulmonary hypertension [ICD11: BB01] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 588.3 Topological Polar Surface Area 137
Heavy Atom Count 32 Rotatable Bond Count 11
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 10
Cross-matching ID
PubChem CID
16004692
PubChem SID
24380756 ; 28680076 ; 37128307 ; 135262332 ; 135626853 ; 136023841 ; 139257646 ; 152256091 ; 152258558 ; 160647393 ; 160703277 ; 162202062 ; 163344650 ; 171572070 ; 172087019 ; 172096639 ; 174007274 ; 175427162 ; 178103924 ; 184815478 ; 189628674 ; 198971703 ; 198993773 ; 223385903 ; 223701845 ; 223705199 ; 227656403 ; 241382239 ; 242590074 ; 248261348 ; 249867527 ; 250225136 ; 252069311 ; 252110242 ; 252166931 ; 252225701 ; 252437394 ; 252451827
ChEBI ID
CHEBI:76607
CAS Number
441798-33-0
TTD Drug ID
D0S7JH
Formula
C19H20Br2N6O4S
Canonical SMILES
CCCNS(=O)(=O)NC1=C(C(=NC=N1)OCCOC2=NC=C(C=N2)Br)C3=CC=C(C=C3)Br
InChI
1S/C19H20Br2N6O4S/c1-2-7-26-32(28,29)27-17-16(13-3-5-14(20)6-4-13)18(25-12-24-17)30-8-9-31-19-22-10-15(21)11-23-19/h3-6,10-12,26H,2,7-9H2,1H3,(H,24,25,27)
InChIKey
JGCMEBMXRHSZKX-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
Aprocitentan DM006455
25099191
Oxidation - Depropylation 1 [2]
Macitentan metabolite M3 DM006458
67041378
Hydrolysis - Hydrolysis 1 [2]
Macitentan metabolite M4 DM006452
70813943
Oxidation - Oxidationn 1 [2]
Macitentan metabolite M7 DM006459 N. A. Oxidation - Hydrolyzationn 1 [2]
Macitentan metabolite M1 DM006457
138455029
Conjugation - Glycosylation 2 [2]
Macitentan metabolite M2 DM006456 N. A. Multi-steps Reaction - Hydrolysis; hydroxylation 2 [2]
Macitentan metabolite M3 DM006458
67041378
Hydrolysis - Hydrolysis 2 [2]
Macitentan metabolite M5 DM006453
129011924
Oxidation - Oxidationn 2 [2]
Macitentan metabolite M324 DM006454 N. A. Hydrolysis - Hydrolysis 3 [2]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006934 Macitentan Macitentan metabolite M4 Oxidation - Oxidationn CYP2C9 [2]
MR006937 Macitentan Aprocitentan Oxidation - Depropylation CYP3A4 ... [2]
MR006941 Macitentan Macitentan metabolite M3 Hydrolysis - Hydrolysis Unclear [2]
MR006942 Macitentan Macitentan metabolite M7 Oxidation - Hydrolyzationn CYP2C8 ... [2]
MR006938 Aprocitentan Macitentan metabolite M2 Multi-steps Reaction - Hydrolysis; hydroxylation Unclear [2]
MR006939 Aprocitentan Macitentan metabolite M1 Conjugation - Glycosylation Unclear [2]
MR006940 Aprocitentan Macitentan metabolite M3 Hydrolysis - Hydrolysis Unclear [2]
MR006935 Macitentan metabolite M4 Macitentan metabolite M5 Oxidation - Oxidationn Unclear [2]
MR006936 Macitentan metabolite M5 Macitentan metabolite M324 Hydrolysis - Hydrolysis Unclear [2]
⏷ Show the Full List of 9 MR(s)
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
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]
Mephenytoin 4-hydroxylase (CYP2C19) DME0021 Homo sapiens
CP2CJ_HUMAN
1.14.14.1
[3]
References
1 Macitentan was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Clinical pharmacokinetics and pharmacodynamics of the endothelin receptor antagonist macitentan
3 Investigation of the effects of ketoconazole on the pharmacokinetics of macitentan, a novel dual endothelin receptor antagonist, in healthy subjects. Clin Pharmacokinet. 2013 Aug;52(8):685-92.

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