•Atomic structures of human ?-secretase bound to inhibitors and the modulator E2012•Differential recognition clinical candidates Semagacestat Avagacestat•Differential transition state analog (TSA) L685,458 non-TSA•Identification allosteric binding site E2012 Development (GSIs) modulators (GSMs) represents an attractive therapeutic opportunity for Alzheimer’s disease (AD) cancers. However, how t...
