Degrading Cell Surface Targets.

New small molecule degrader DeDPP4 reduces dipeptidyl peptidase-4 protein levels and prolongs glucose lowering compared to alogliptin, supporting targeted protein degradation as a novel strategy for durable metabolic control. A full mechanistic understanding of how a system relying on intracellular degradation can act on a cell-surface protein will be instrumental in guiding the rational development of new degraders for this class of targets.