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

Shinichi Sato, Masashi Tetsuhashi, Keiko Sekine, Hiroyuki Miyachi, Mikihiko Naito, Yuichi Hashimoto, Hiroshi Aoyama

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 α-position of the internal amide carbonyl group, and the presence of a small substituent at the α-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 (IC50 = 0.53 μM) among the compounds prepared.

Original languageEnglish
Pages (from-to)4685-4698
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number8
DOIs
Publication statusPublished - Apr 15 2008

Keywords

  • Actinonin
  • Bestatin
  • Inhibitor
  • Structural development
  • cIAP1

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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  • Cite this

    Sato, S., Tetsuhashi, M., Sekine, K., Miyachi, H., Naito, M., Hashimoto, Y., & Aoyama, H. (2008). Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. Bioorganic and Medicinal Chemistry, 16(8), 4685-4698. https://doi.org/10.1016/j.bmc.2008.02.024