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ID: ALA1136833

Journal: Bioorg Med Chem Lett

Title: Novel non-peptide inhibitors targeting death receptor-mediated apoptosis.

Authors: Kakeya H, Miyake Y, Shoji M, Kishida S, Hayashi Y, Kataoka T, Osada H.

Abstract: We have previously reported that ECH, (2R, 3R, 4S)-2,3-epoxy-4-hydroxy-5-hydroxymethyl-6-(1E)-propenyl-cyclohex-5-en-1-one inhibits Fas-mediated apoptosis by blocking self-activation of pro-caspase-8 in the death-inducing signaling complex (DISC). A series of ECH derivatives were asymmetrically synthesized via key synthetic intermediates obtained from lipase-catalyzed kinetic resolution. Inhibitory activities of the derivatives towards death receptor-mediated apoptosis both in type I and type II cells were investigated, revealing that novel non-peptide inhibitors, RKTS-33 and RKTS-34, are effective as ECH.

CiteXplore: 14552771

DOI: 10.1016/j.bmcl.2003.08.003