Preclinical Pharmacokinetics Study Of A Novel Hsp90 Inhibitor-SNX-2112

SNX-2112 is a novel screened Hsp90 inhibitor in recent years, Many experiments, both in vivo and in vitro, have proved its significant antitumor effect. Currently SNX-2112 is considered to be a promising anti-cancer drug for exploring.The work developed in this dissertation were as follows:1. Developed a method for the determination of SNX-2112.2. Developed a method for determination of SNX-2112 in the biological samples.3. The pharmacokinetics of SNX-2112 were studied. The results showed that the pharmaco-kinetics of SNX-2112 in rats plasma agreed with two-compartment model. After i.v. administration of SNX-2112 with 10 mg/kg, the terminate half-life of SNX-2112 was 10.41±4.38h. The parameters of another two dosage groups (2.5 mg/kg,5 mg/kg) were similar.The distribution study of SNX-2112 in rats showed that SNX-2112 could be extensively after i.v. administration with 10mg/kg, and it is distributed in liver at most. After i.v. administration with 10mg/kg, the samples of urine, and bile in rats were analyzed by HPLC. The study showed that the origin form of SNX-2112 was mainly excreted via fece. The experiment also measured the effects of SNX-2112 on hepatic drug metabolizing enzymes. In addition, this study also measured plasma protein binding rates of SNX-2112 with rat plasma and human plasma using ultrafiltration, the metabolism of SNX-2112 has been done a preliminary study.These experiments of the compound provided a scientific basis for clinical research in the future.