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 journalArticle

20 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 languageEnglish
Pages (from-to)3743-3746
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number21
DOIs
Publication statusPublished - 2003 Nov 3
Externally publishedYes

Fingerprint

Death Domain Receptors
Death Domain Receptor Signaling Adaptor Proteins
Apoptosis
Derivatives
Caspase 8
Lipase
Chemical activation
Kinetics

ASJC Scopus subject areas

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

Cite this

Kakeya, H., Miyake, Y., Shoji, M., Kishida, S., Hayashi, Y., Kataoka, T., & Osada, H. (2003). Novel non-peptide inhibitors targeting death receptor-mediated apoptosis. Bioorganic and Medicinal Chemistry Letters, 13(21), 3743-3746. https://doi.org/10.1016/j.bmcl.2003.08.003

Novel non-peptide inhibitors targeting death receptor-mediated apoptosis. / Kakeya, Hideaki; Miyake, Yasunobu; Shoji, Mitsuru; Kishida, Satoshi; Hayashi, Yujiro; Kataoka, Takao; Osada, Hiroyuki.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 13, No. 21, 03.11.2003, p. 3743-3746.

Research output: Contribution to journalArticle

Kakeya, H, Miyake, Y, Shoji, M, Kishida, S, Hayashi, Y, Kataoka, T & Osada, H 2003, 'Novel non-peptide inhibitors targeting death receptor-mediated apoptosis', Bioorganic and Medicinal Chemistry Letters, vol. 13, no. 21, pp. 3743-3746. https://doi.org/10.1016/j.bmcl.2003.08.003
Kakeya, Hideaki ; Miyake, Yasunobu ; Shoji, Mitsuru ; Kishida, Satoshi ; Hayashi, Yujiro ; Kataoka, Takao ; Osada, Hiroyuki. / Novel non-peptide inhibitors targeting death receptor-mediated apoptosis. In: Bioorganic and Medicinal Chemistry Letters. 2003 ; Vol. 13, No. 21. pp. 3743-3746.
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