CPI-8

CPI-8 is a small molecule transcriptional inhibitor of CYP24A1, the primary enzyme responsible for the catabolism of 1,25-dihydroxyvitamin D3 (1,25D3). Identified through a high-throughput screen of the DIVERSet library by researchers at Roswell Park Cancer Institute, CPI-8 was selected for its potent ability to suppress 1,25D3-induced CYP24A1 expression at the mRNA and protein levels. By inhibiting this degradation pathway, CPI-8 aims to maintain therapeutic concentrations of Vitamin D within the tumor microenvironment, thereby enhancing its anti-proliferative and pro-apoptotic effects. Preclinical studies in prostate, bladder, and kidney cancer cell lines have shown that CPI-8 not only reduces CYP24A1 but also upregulates the expression of the cyclin-dependent kinase inhibitor p21Waf1, further contributing to its potential anti-tumor efficacy.