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

• Publication year

  2020

• Venue

  European journal of medicinal chemistry

• Publication date

  2020-12-11

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.ejmech.2020.113053PMID 33359953
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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