AU-22880

AU-22880 is an orally bioavailable, highly potent, and selective reversible covalent inhibitor of cyclin-dependent kinase 12 (CDK12) being developed by Aurigene Oncology for the treatment of various cancers. CDK12, in association with Cyclin K, regulates transcription elongation by phosphorylating RNA polymerase II (RNAP II) at Serine 2 (pS2), thereby maintaining genomic stability and modulating DNA damage response (DDR) pathways. By selectively inhibiting CDK12, AU-22880 demonstrates significant anti-proliferative activity across multiple cancer cell lines and exhibits synergistic effects when combined with standard-of-care agents targeting the DDR pathway. In preclinical models, including triple-negative breast cancer (TNBC) xenografts, AU-22880 has shown robust anti-tumor efficacy and dose-dependent target engagement with a favorable tolerability profile.