1. Academic Validation
  2. Lysine Covalent Antagonists of Melanoma Inhibitors of Apoptosis Protein

Lysine Covalent Antagonists of Melanoma Inhibitors of Apoptosis Protein

  • J Med Chem. 2021 Nov 11;64(21):16147-16158. doi: 10.1021/acs.jmedchem.1c01459.
Parima Udompholkul 1 Carlo Baggio 1 Luca Gambini 1 Giulia Alboreggia 1 Maurizio Pellecchia 1
Affiliations

Affiliation

  • 1 Division of Biomedical Sciences, School of Medicine, University of California Riverside, 900 University Avenue, Riverside, California 92521, United States.
Abstract

We have recently reported on Lys-covalent agents that, based on aryl-sulfonyl fluorides, were designed to target binding site Lys 311 in the X-linked inhibitor of Apoptosis protein (XIAP). Similar to XIAP, melanoma-IAP (ML-IAP), a less well-characterized IAP family protein, also presents a lysine residue (Lys 135), which is in a position equivalent to that of Lys 311 of XIAP. On the contrary, two other members of the IAP family, namely, cellular-IAPs (cIAP1 and cIAP2), present a glutamic acid residue in that position. Hence, in the present work, we describe the derivation and characterization of the very first potent ML-IAP Lys-covalent inhibitor with cellular activity. The agent can be used as a pharmacological tool to further validate ML-IAP as a drug target and eventually for the development of ML-IAP-targeted therapeutics.

Figures
Products