Novel non-peptide inhibitors targeting death receptor-mediated apoptosis

Hideaki Kakeya; Yasunobu Miyake; Mitsuru Shoji; Satoshi Kishida; Yujiro Hayashi; Takao Kataoka; Hiroyuki Osada

doi:10.1016/j.bmcl.2003.08.003

Novel non-peptide inhibitors targeting death receptor-mediated apoptosis

Hideaki Kakeya, Yasunobu Miyake, Mitsuru Shoji, Satoshi Kishida, Yujiro Hayashi, Takao Kataoka, Hiroyuki Osada

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3743-3746
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2003.08.003
Publication status	Published - 2003 Nov 3
Externally published	Yes

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2003.08.003

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title = "Novel non-peptide inhibitors targeting death receptor-mediated apoptosis",

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.",

author = "Hideaki Kakeya and Yasunobu Miyake and Mitsuru Shoji and Satoshi Kishida and Yujiro Hayashi and Takao Kataoka and Hiroyuki Osada",

note = "Funding Information: This work was supported in part by a Special Project Funding for Basic Science (Chemical Biology Research) from RIKEN, and a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.",

year = "2003",

month = nov,

day = "3",

doi = "10.1016/j.bmcl.2003.08.003",

language = "English",

volume = "13",

pages = "3743--3746",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "21",

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TY - JOUR

T1 - Novel non-peptide inhibitors targeting death receptor-mediated apoptosis

AU - Kakeya, Hideaki

AU - Miyake, Yasunobu

AU - Shoji, Mitsuru

AU - Kishida, Satoshi

AU - Hayashi, Yujiro

AU - Kataoka, Takao

AU - Osada, Hiroyuki

N1 - Funding Information: This work was supported in part by a Special Project Funding for Basic Science (Chemical Biology Research) from RIKEN, and a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

PY - 2003/11/3

Y1 - 2003/11/3

N2 - 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.

AB - 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.

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DO - 10.1016/j.bmcl.2003.08.003

M3 - Article

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AN - SCOPUS:0141656406

SN - 0960-894X

VL - 13

SP - 3743

EP - 3746

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Novel non-peptide inhibitors targeting death receptor-mediated apoptosis

Abstract

ASJC Scopus subject areas

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