2. Academic Validation
  3. Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin

Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin

  • Bioorg Med Chem. 2008 Apr 15;16(8):4685-98. doi: 10.1016/j.bmc.2008.02.024.
Shinichi Sato 1,  Masashi Tetsuhashi,  Keiko Sekine,  Hiroyuki Miyachi,  Mikihiko Naito,  Yuichi Hashimoto,  Hiroshi Aoyama
Affiliations

Affiliation

  • 1 Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Tokyo 113-0032, Japan.
PMID: 18313309 DOI: 10.1016/j.bmc.2008.02.024
Abstract

A series of hybrid compounds of bestatin (1) and actinonin (3), which promote degradation of cellular inhibitor of Apoptosis protein 1 (cIAP1), were designed and synthesized. Structure-activity relationship studies indicated that absolute configuration, hydrophobicity at the alpha-position of the internal amide carbonyl group, and the presence of a small substituent at the alpha-position of the ester group are important factors for the expression of potent cIAP1 degradation-promoting activity. HAB-5A (30b) showed the most potent activity (IC(50)=0.53 microM) among the compounds prepared.

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