Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 2.1.1.9 extracted from

  • Liu, C.; Chen, Z.; Zhong, K.; Li, L.; Zhu, W.; Chen, X.; Zhong, D.
    Human liver cytochrome P450 enzymes and microsomal thiol methyltransferase are involved in the stereoselective formation and methylation of the pharmacologically active metabolite of clopidogrel (2015), Drug Metab. Dispos., 43, 1632-1641.
    View publication on PubMed

Application

Application Comment Organism
medicine clopidogrel, a thienopyridine antiplatelet prodrug, is metabolized by oxidation to 2-oxo-clopidogrel, followed by conversion to its pharmacologically active thiol metabolite. In liver microsomes, thiol isomers H3 and H4 are further S-methylated, and the S-methylation is inhibited by 2,3-dichloromethyl benzylamine, indicating the involvement of thiol S-methyltransferase. The intrinsic clearance value for the S-methylation of H3 in microsomes is 98.1fold higher than that for H4. The stereoselective formation of H3 from 2-oxo-clopidogrel and the stereoselective S-methylation of H3 may lead to the similar exposure levels of H3 and H4 previously reported in humans Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
2,3-dichloromethyl benzylamine
-
Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
microsome
-
Homo sapiens
-
-

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
liver
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(2Z)-[(4R)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid + S-adenosyl-L-methionine thiol metabolite H4 of prodrug clopidogrel. The intrinsic clearance value for the S-methylation of metabolite H3 in microsomes is 98.1fold higher than that for H4 Homo sapiens (2Z)-[(4R)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-(methylsulfanyl)piperidin-3-ylidene]acetic acid + S-adenosyl-L-homocysteine
-
?
(2Z)-[(4S)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-sulfanylpiperidin-3-ylidene]acetic acid + S-adenosyl-L-methionine thiol metabolite H3 of prodrug clopidogrel. The intrinsic clearance value for the S-methylation of metabolite H3 in microsomes is 98.1fold higher than that for H4 Homo sapiens (2Z)-[(4S)-1-[(1S)-1-(2-chlorophenyl)-2-methoxy-2-oxoethyl]-4-(methylsulfanyl)piperidin-3-ylidene]acetic acid + S-adenosyl-L-homocysteine
-
?