Mori, K. published the artcileCocktail-substrate assay system for mechanism-based inhibition of CYP2C9, CYP2D6, and CYP3A using human liver microsomes at an early stage of drug development, Synthetic Route of 40180-04-9, the main research area is cocktail substrate assay cytochrome P450 liver microsome drug development.
1. We established a mechanism-based inhibition cocktail-substrate assay system using human liver microsomes and drugprobe substrates that enabled simultaneous estimation of the inactivation of main cytochrome P 450 (CYP) enzymes, CYP2C9, CYP2D6, and CYP3A, in drug metabolism 2. The inactivation kinetic parameters of typical mechanism-based inhibitors, tienilic acid, paroxetine, and erythromycin, for each enzyme in the cocktail-substrate assay were almost in agreement with the values obtained in the single-substrate assay. 3. Using this system, we confirmed that multiple CYP inactivation caused by mechanism-based inhibitors such as isoniazid and amiodarone could be detected simultaneously. 4. Mechanism-based inhibition potency can be estimated by the determination of the observed inactivation rate constants (kobs) at a single concentration of test compounds because the kobs of eleven CYP3A inactivators at 10×M in the assay system nearly corresponded to kinact/KI values, an indicator of a compound’s propensity to alter the activity of a CYP in vivo (R2 = 0.97). 5 Therefore, this cocktail-substrate assay is considered to be a powerful tool for evaluating mechanism-based inhibition at an early stage of drug development.
Xenobiotica published new progress about Combination chemotherapy. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Synthetic Route of 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem