PXG-CycK

PXG-CycK is an investigational small-molecule molecular glue degrader that selectively induces proteasomal degradation of Cyclin K, thereby functionally suppressing CDK12/Cyclin K–dependent transcriptional programs in cancer cells. Preclinical data presented at the AACR-NCI-EORTC 2025 Molecular Targets meeting show that PXG-CycK has a best-in-class Cyclin K degradation profile, exceptional selectivity against other cyclin-dependent kinases, and potent antitumor activity, including tumor regressions as a single agent in HER2-amplified breast cancer xenograft models without significant adverse effects.[4][7][1] By exploiting transcriptional vulnerabilities and homologous recombination repair defects, PXG-CycK is being advanced by Proxygen toward clinical development for HER2-positive breast cancer and other CDK12/Cyclin K–dependent or homologous repair–deficient solid tumors such as triple-negative breast cancer and ovarian cancer.[1][4][5]