Some of the most important targets in cancer, including KRAS and MYC, have thwarted the best efforts of drug developers for decades because their active sites are not amenable to targeting with small molecule inhibitors. Such proteins have become notorious for this “undruggability” yet remain an area of intense focus for drug development because of their therapeutic potential.
Now there is hope on the horizon that small molecules can, after all, target the undruggable. Recent years have witnessed the rise of an exciting new modality – targeted protein degradation (TPD) – that has attracted some $3 billion in investments to date. This . . .