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ID: ALA5096205

Journal: J Med Chem

Title: Lysine Covalent Antagonists of Melanoma Inhibitors of Apoptosis Protein.

Authors: Udompholkul P, Baggio C, Gambini L, Alboreggia G, Pellecchia M.

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.

CiteXplore: 34705456

DOI: 10.1021/acs.jmedchem.1c01459