Insilico Medicine has published the discovery of a first-in-class PROTAC drug candidate targeting PKMYT1—a kinase implicated in cell‑cycle regulation and synthetic‑lethality vulnerabilities in certain cancers.
Using its generative AI drug‑discovery platform Chemistry42, the company began by designing a novel PKMYT1 inhibitor, generating over 2,000 candidate molecules. After medicinal‑chemistry optimization and structure‑based modelling, the researchers linked the inhibitor to an E3‑ligase binder—creating a proteolysis‑targeting chimera (PROTAC) dubbed D16-M1P2.
The key feature of D16‑M1P2 is its dual mechanism: it both degrades PKMYT1 via the ubiquitin‑proteasome system and directly inhibits remaining kinase activity at higher concentration, providing a more robust and durable blockade of the target. In preclinical studies, the molecule showed high selectivity—inhibiting only 4 out of 403 kinases tested—and demonstrated potent anti‑tumor effects in xenograft models, with favorable oral bioavailability and sustained pharmacodynamic activity even after drug removal.
According to Insilico, this work showcases the power of AI‑driven drug design not only to identify novel targets, but also to generate entirely new molecules—including complex multi‑component therapeutics like PROTACs—in a compact timeframe. The company has advanced D16-M1P2 to the Pre‑Candidate Validation stage, marking a significant milestone for AI‑enabled oncology drug discovery.
