KP-457 is a potent, selective ADAM17 inhibitor with IC50 of 11.1 nM, >50 times more selective for ADAM17 than for other MMPs and ADAM10. KP-457 blocks Zn2+ chelation of the catalytic domain of ADAM17. KP‐457 blocks GPIbα shedding from iPSC platelets at a lower half‐maximal inhibitory concentration than panmetalloproteinase inhibitor GM‐6001. KP‐457 exhibits improved GPIbα‐dependent aggregation not inferior to human fresh platelets. KP-457 effectively enhances the production of functional human iPSC‐derived platelets at 37°C.
