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

General Information of Drug (ID: DR0222)
Drug Name
Bosentan
Synonyms
Bosentan; Bosentan [USAN:INN:BAN]; Actelion; Ro 47-0203; Ro 47-0203/039; Ro-47-0203; Tracleer; XUL93R30K2; bosentanum; 147536-97-8; 4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl)benzenesulfornamide; 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide; C27H29N5O6S; CHEBI:51450; CHEMBL957; UNII-XUL93R30K2; p-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide
Indication Pulmonary hypertension [ICD11: BB01] Approved [1]
Structure
3D MOL 2D MOL
Pharmaceutical Properties Molecular Weight 551.6 Topological Polar Surface Area 154
Heavy Atom Count 39 Rotatable Bond Count 11
Hydrogen Bond Donor Count 2 Hydrogen Bond Acceptor Count 11
Cross-matching ID
PubChem CID
104865
PubChem SID
7978805 ; 10233650 ; 12014838 ; 14763764 ; 44434454 ; 46507154 ; 47285934 ; 48179783 ; 49831038 ; 49881484 ; 50112694 ; 50840650 ; 51091861 ; 53787963 ; 56464382 ; 57337889 ; 85209778 ; 92309270 ; 92714194 ; 93581179 ; 93619683 ; 103250068 ; 103956688 ; 104179184 ; 104373115 ; 118855338 ; 125341362 ; 126592988 ; 126624339 ; 126655593 ; 126671144 ; 127344134 ; 127344135 ; 127344136 ; 127963291 ; 131299472 ; 134337358 ; 134339787 ; 135143300 ; 135723687 ; 137003210 ; 142094009 ; 143493318 ; 144115748 ; 144205997 ; 151991482 ; 152237729 ; 152258948 ; 160647793 ; 160963904
ChEBI ID
ChEBI:51450
CAS Number
147536-97-8
TTD Drug ID
D0U4CE
Formula
C27H29N5O6S
Canonical SMILES
CC(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC2=C(C(=NC(=N2)C3=NC=CC=N3)OCCO)OC4=CC=CC=C4OC
InChI
1S/C27H29N5O6S/c1-27(2,3)18-10-12-19(13-11-18)39(34,35)32-23-22(38-21-9-6-5-8-20(21)36-4)26(37-17-16-33)31-25(30-23)24-28-14-7-15-29-24/h5-15,33H,16-17H2,1-4H3,(H,30,31,32)
InChIKey
GJPICJJJRGTNOD-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
Bosentan metabolite Ro 47-8634 DM001446
6426756
Oxidation - O-Demethylation 1 [4]
Bosentan metabolite Ro 48-5033 DM001449
6426755
Oxidation - Methyl-Hydroxylation 1 [4]
Bosentan metabolite Ro 64-1056 DM001447
6426757
Oxidation - O-Demethylation 2 [4]
Bosentan metabolite Ro 64-1056 DM001447
6426757
Oxidation - Methyl-Hydroxylation 2 [4]
Bosentan metabolite M4 DM001448 N. A. Unclear 3 [4]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR000416 Bosentan Bosentan metabolite Ro 47-8634 Oxidation - O-Demethylation CYP3A4 ... [4]
MR000417 Bosentan Bosentan metabolite Ro 48-5033 Oxidation - Methyl-Hydroxylation CYP3A4 ... [4]
MR000413 Bosentan metabolite Ro 47-8634 Bosentan metabolite Ro 64-1056 Oxidation - Methyl-Hydroxylation Unclear [4]
MR000415 Bosentan metabolite Ro 48-5033 Bosentan metabolite Ro 64-1056 Oxidation - O-Demethylation Unclear [4]
MR000414 Bosentan metabolite Ro 64-1056 Bosentan metabolite M4 Unclear Unclear [4]
Drug-Metabolizing Enzyme(s) (DME) Metabolizing This Drug
DME Name DME Info Species Uniprot ID EC Number REF
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]
References
1 Macitentan was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301.
3 Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
4 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.

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