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

doi:10.1016/j.bmc.2008.02.024

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 journal › Article › peer-review

21 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 language	English
Pages (from-to)	4685-4698
Number of pages	14
Journal	Bioorganic and Medicinal Chemistry
Volume	16
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2008.02.024
Publication status	Published - Apr 15 2008
Externally published	Yes

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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10.1016/j.bmc.2008.02.024

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title = "Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin",

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.",

keywords = "Actinonin, Bestatin, Inhibitor, Structural development, cIAP1",

author = "Shinichi Sato and Masashi Tetsuhashi and Keiko Sekine and Hiroyuki Miyachi and Mikihiko Naito and Yuichi Hashimoto and Hiroshi Aoyama",

note = "Funding Information: The authors are grateful to Prof. Aya Tanatani (Ochanomizu University) for her helpful discussion. The work described in this paper was partially supported by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the promotion of Science.",

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doi = "10.1016/j.bmc.2008.02.024",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry",

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T1 - Degradation-promoters of cellular inhibitor of apoptosis protein 1 based on bestatin and actinonin

AU - Sato, Shinichi

AU - Tetsuhashi, Masashi

AU - Sekine, Keiko

AU - Miyachi, Hiroyuki

AU - Naito, Mikihiko

AU - Hashimoto, Yuichi

AU - Aoyama, Hiroshi

N1 - Funding Information: The authors are grateful to Prof. Aya Tanatani (Ochanomizu University) for her helpful discussion. The work described in this paper was partially supported by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for the promotion of Science.

PY - 2008/4/15

Y1 - 2008/4/15

N2 - 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.

AB - 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.

KW - Actinonin

KW - Bestatin

KW - Inhibitor

KW - Structural development

KW - cIAP1

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DO - 10.1016/j.bmc.2008.02.024

M3 - Article

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AN - SCOPUS:42149103458

SN - 0968-0896

VL - 16

SP - 4685

EP - 4698

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 8

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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