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

General Information of Drug (ID: DR0984)
Drug Name
Losartan potassium
Synonyms
Losartan [INN:BAN]; Losartan monopotassium salt; losartan; (2-butyl-4-chloro-1-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-imidazol-5-yl)methanol; 114798-26-4; 2-Butyl-4-chloro-1-((2'-(1H-etrazol-5-yl) (1,1'-biphenyl)-4-yl)methyl)-1H-imidazole-5-methanol; C22H23ClN6O; CHEBI:6541; MFCD00865831; UNII-JMS50MPO89; [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol; DUP 89; JMS50MPO89; Lifezar; Lorzaan; Lorzaar; Losacar; Losacor; Losaprex; Losartan Potassium (DuP 753); MK 0954; MK 954; MK-0954; Neo Lotan; Ocsaar; Tenopres; losartan potassium salt; losartanpotassium; 124750-99-8; 2-Butyl-4-chloro-1-(2'-(tetrazol-5-yl)biphenyl-4-ylmethyl)-1H-imidazole-5-methanol potassium; 3ST302B24A; C22H22CIKN6OK; Lotim; Niten; UNII-3ST302B24A; Du Pont 753; ERYTHROPOIETIN; L-158086
Indication Essential hypertension [ICD11: BA00] Approved [1]
Structure
3D MOL is unavailable 2D MOL
Pharmaceutical Properties Molecular Weight 461 Topological Polar Surface Area 77.7
Heavy Atom Count 31 Rotatable Bond Count 8
Hydrogen Bond Donor Count 1 Hydrogen Bond Acceptor Count 6
Cross-matching ID
PubChem CID
11751549
CAS Number
864750-70-9
TTD Drug ID
D0DD0K
Formula
C22H22ClKN6O
Canonical SMILES
CN(CCN1CCC(CC1)OC(=O)NC2=CC=CC=C2C3=CC=CC=C3)C(=O)C4=CC=C(C=C4)CN5CCC(CC5)C(=O)N
InChI
1S/C35H43N5O4/c1-38(34(42)29-13-11-26(12-14-29)25-40-19-15-28(16-20-40)33(36)41)23-24-39-21-17-30(18-22-39)44-35(43)37-32-10-6-5-9-31(32)27-7-3-2-4-8-27/h2-14,28,30H,15-25H2,1H3,(H2,36,41)(H,37,43)
InChIKey
OXCMYAYHXIHQOA-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
Losartan Carboxaldehyde DM006434
9802264
Oxidation - Oxidationn 1 [6]
Losartan carboxylic acid DM006435
108185
Oxidation - N-oxidation 1 [6]
Losartan N2-glucuronide DM006436
49849772
Conjugation - N-glucuronidation 1 [6]
Losartan carboxylic acid DM006435
108185
Unclear 2 [3]
The Full List of Metabolic Reaction (MR) of This Drug
MR ID Reactant Product MR Type DME REF
MR006913 Losartan potassium Losartan Carboxaldehyde Oxidation - Oxidationn CYP3A4 ... [6]
MR006915 Losartan potassium Losartan N2-glucuronide Conjugation - N-glucuronidation UGT1A1 ... [6]
MR006916 Losartan potassium Losartan carboxylic acid Oxidation - N-oxidation CYP3A4 ... [6]
MR006914 Losartan Carboxaldehyde Losartan carboxylic acid Unclear CYP3A4 ... [3]
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
[3]
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]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DME0004 Homo sapiens
UD11_HUMAN
2.4.1.17
[5]
UDP-glucuronosyltransferase 1A10 (UGT1A10) DME0075 Homo sapiens
UD110_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 1A3 (UGT1A3) DME0041 Homo sapiens
UD13_HUMAN
2.4.1.17
[3]
UDP-glucuronosyltransferase 2B17 (UGT2B17) DME0066 Homo sapiens
UDB17_HUMAN
2.4.1.17
[6]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DME0040 Homo sapiens
UD2B7_HUMAN
2.4.1.17
[3]
Unclear metabolic mechanism (DME-unclear) DME1251 Bacteroides fragilis Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1256 Bacteroides sartorii Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1365 Bacteroides dorei Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1384 Bacteroides vulgatus Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1385 Bacteroides xylanisolvens Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1391 Bifidobacterium ruminatum Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1444 Odoribacter splanchnicus Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1445 Parabacteroides distasonis Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1446 Parabacteroides johnsonii Not Available Not Available [7]
Unclear metabolic mechanism (DME-unclear) DME1447 Parabacteroides merdae Not Available Not Available [7]
⏷ Show the Full List of 19  DME(s)
References
1 Losartan Potassium was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
2 Drug-drug interaction between losartan and paclitaxel in human liver microsomes with different CYP2C8 genotypes. Basic Clin Pharmacol Toxicol. 2015 Jun;116(6):493-8.
3 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.
4 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
5 The human UDP-glucuronosyltransferase UGT1A3 is highly selective towards N2 in the tetrazole ring of losartan, candesartan, and zolarsartan. Biochem Pharmacol. 2008 Sep 15;76(6):763-72.
6 Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814.
7 Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019 Jun;570(7762):462-467.

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