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

15 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
Externally publishedYes

Fingerprint

Inhibitor of Apoptosis Proteins
Degradation
Structure-Activity Relationship
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Amides
Proteolysis
Inhibitory Concentration 50
Esters
ubenimex
actinonin

Keywords

  • Actinonin
  • Bestatin
  • cIAP1
  • Inhibitor
  • Structural development

ASJC Scopus subject areas

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

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

Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. / Sato, Shinichi; Tetsuhashi, Masashi; Sekine, Keiko; Miyachi, Hiroyuki; Naito, Mikihiko; Hashimoto, Yuichi; Aoyama, Hiroshi.

In: Bioorganic and Medicinal Chemistry, Vol. 16, No. 8, 15.04.2008, p. 4685-4698.

Research output: Contribution to journalArticle

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, vol. 16, no. 8, pp. 4685-4698. https://doi.org/10.1016/j.bmc.2008.02.024
Sato, Shinichi ; Tetsuhashi, Masashi ; Sekine, Keiko ; Miyachi, Hiroyuki ; Naito, Mikihiko ; Hashimoto, Yuichi ; Aoyama, Hiroshi. / Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin. In: Bioorganic and Medicinal Chemistry. 2008 ; Vol. 16, No. 8. pp. 4685-4698.
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