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 | Comment | Organism | Structure |
---|---|---|---|
2,3-dichloromethyl benzylamine | - |
Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
microsome | - |
Homo sapiens | - |
- |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
liver | - |
Homo sapiens | - |
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 | - |
? |