Breaking Barriers in Cancer Therapy: AI-Designed PROTAC Targets PKMYT1
Cancer cells often rely on “backup systems” to survive when their cell cycle controls fail. One such system involves PKMYT1, a protein that helps regulate when cells divide. In some cancers—especially those with genetic changes like CCNE1 amplification or mutations in FBXW7 and PPP2R1A—PKMYT1 becomes essential for tumour growth. Removing PKMYT1 kills these cancer cells while sparing healthy ones, a process called synthetic lethality.
Existing PKMYT1 inhibitors suffer from poor selectivity and side effects. To overcome this, Insilico Medicine Shanghai Ltd and Insilico Medicine Hong Kong Ltd used macromolecular crystallography (MX) at Diamond to determine PKMYT1’s 3D structure, then applied AI to design and optimise a new drug called a PROTAC. Unlike traditional drugs that simply block a protein, PROTACs tag the protein for destruction inside the cell.
The result? D16-M1P2, a bifunctional PROTAC that combines a novel PKMYT1 blocker with a component that recruits the cell’s own disposal system (via cereblon, an E3 ligase). This means the drug both inhibits PKMYT1’s activity and removes PKMYT1 completely.