Pharmacodynamics of Cyclin D1 Degradation in Ovarian Cancer Xenografts with Repeated Oral SHetA2 Dosing.

ABSTRACT: SHetA2 is a promising, orally active small molecule with anticancer properties that target heat shock proteins. In this study, we aimed to investigate the pharmacodynamic (PD) effects of SHetA2 using preclinical in vitro and in vivo models of ovarian cancer and establish a physiologically based pharmacokinetic (PBPK)/PD model to describe their relationships with SHetA2 concentrations in mice. We found that daily oral administration of 60 mg/kg SHetA2 for 7 days resulted in consistent plasma PK and tissue distribution, achieving tumor drug concentrations required for growth inhibition in ovarian cancer cell lines. SHetA2 effectively induced cyclin D1 degradation in cancer cells in a dose-dependent manner, with up to 70% reduction observed and an IC₅₀ of 4~5 µM. We identified cycl

SUBMITTER: Sharma A 

PROVIDER: S-EPMC11610768 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature