Modulators of hERAP2 discovered by high-throughput screening

Endoplasmic reticulum aminopeptidase 2, ERAP2, is an emerging pharmacological target in cancer immunotherapy and control of autoinflammatory diseases, as it involved antigen processing. It has been linked to the risk development spondyloarthritis, associates with immune infiltration tumours strongly predicts overall survival for patients receiving check-point inhibitor therapy. While some selective inhibitors its homolog ERAP1 are available, no modulator ERAP2 disclosed so far. In order identify such compounds, we screened in-house focused library 1920 compounds designed metalloenzymes. Structure-Activity Relationships docking around two hits led discovery ERAP2. Amid those, bind yet untapped amino-acids S1 pocket. Importantly, disclose also first activator small substrates hydrolysis by Inhibitors activators identified this study could serve useful starting points optimization.