The effects of a novel Hsp90 inhibitor - SNX-2112 on hepatis metablic enzymes in rats

Aim: To investigate the effects of SNX-2112 injection on rat' s hepatic metablic enzymes. Method: Rats were divided into seven groups, they are phenobarbital group, CCl4 group, SNX-2112 high, medium and low (10 mg · kg-1, 5 mg · kg-1, 2.5 mg · kg -1) dose group, the physiological saline control group, and the menstruum group. After being administered the drug through vein for three times, the liver microsomes of rats were distilled by CaCl2 precipitation velocity centrifugation. A UV method was used to detect content of cytochrome P450 in liver microsomes, and the activities of some CYP450 in rats was studied by spectrophotometer. Result: Three dosages of SNX-2112 did not significantly affect rat' liver protein content and liver coefficient, however they all suppressed the CYP450 content. From the results of the formaldehyde production rate, we can see the dosage at 10 mg · kg-1 and 5 mg · kg-1 of SNX-2112 could inhibit rat aminopyrine-N-demethylase activity and erythromycin-N-demethylase activity of rats, while 2.5 mg · kg -1 had no significant effect. Conclusion: SNX-2112 injection at the high concentration can inhibit the activity of CYP3A and CYP2E1 hypotype in rat' hepatic metablic enzymes.