CT7311

CT7311 is a small molecule protein degrader targeting cyclin K, developed by Carrick Therapeutics. By inducing the degradation of cyclin K, CT7311 effectively inhibits the activity of its binding partner, cyclin-dependent kinase 12 (CDK12). This depletion leads to homologous recombination (HR) repair deficiency and induces transcription-replication conflicts (TRCs), a significant source of replication stress. Furthermore, CT7311 impairs the chromatin loading of Replication Protein A (RPA) by disrupting the PRPF19 E3-ligase complex, thereby limiting ATR activation. This mechanism sensitizes tumor cells, particularly triple-negative breast cancer (TNBC) with high MYC expression, to ATR inhibitors and other DNA-damaging agents. Preclinical studies suggest that CT7311 sensitivity does not strictly correlate with HR repair status, extending its potential utility to various replication stress-high tumors.