Conc142

Conc142 is a first-in-class, oral small-molecule molecular glue stabilizer of p27 (CDKN1B), developed by Concarlo Therapeutics. It specifically binds to the trimeric CDK-cyclin-p27 complex, preventing the phosphorylation of p27 at the Y88 residue. This stabilization maintains p27 in an active inhibitory state, leading to the coordinated inhibition of cyclin-dependent kinases CDK2, CDK4, and CDK6. By targeting p27, Conc142 aims to overcome resistance to standard-of-care CDK4/6 inhibitors (like palbociclib) in ER-positive metastatic breast cancer, where bypass via CDK2 activation is common. Preclinical studies demonstrate its efficacy in both treatment-naïve and CDK4/6i-resistant breast cancer models while sparing normal cells.