Johnson, Joshua L. published the artcileOptimal pH 8.5 to 9 for the hydrolysis of vixotrigine and other basic substrates of carboxylesterase-1 in human liver microsomes, Quality Control of 637-07-0, the publication is Xenobiotica (2022), 52(2), 105-112, database is CAplus and MEDLINE.
Vixotrigine is a voltage- and use-dependent sodium channel blocker under investigation for the potential treatment of neuropathic pain. One of the major in vivo metabolic pathways of vixotrigine in humans is the hydrolysis of the carboxamide to form the carboxylic acid metabolite M14. The in vitro formation of M14 in human hepatocytes was inhibited by the carboxylesterase (CES) inhibitor Bis(4-nitrophenyl) phosphate in a concentration-dependent manner. The hydrolysis reaction was identified to be catalyzed by recombinant human CES1b. Initial observation of only trace level formation of M14 in human liver microsomes at pH 7.4 caused us to doubt the involvement of CES1, an enzyme localised at the endoplasmic reticulum and the dominant carboxylesterase in human liver. Further investigation has revealed that optimal pH for the hydrolysis of vixotrigine and two other basic substrates of CES1, methylphenidate and oseltamivir, in human liver microsomes was pH 8.5-9 which is higher than their resp. pKa(base), suggesting that neutral form of basic substrates is probably preferred for CES1 catalysis in liver microsomes.
Xenobiotica published new progress about 637-07-0. 637-07-0 belongs to chlorides-buliding-blocks, auxiliary class Inhibitor,Cell Cycle,PPAR, name is Ethyl 2-(4-chlorophenoxy)-2-methylpropanoate, and the molecular formula is C12H15ClO3, Quality Control of 637-07-0.
Referemce:
https://en.wikipedia.org/wiki/Chloride,
Chlorides – an overview | ScienceDirect Topics