The first Hes1 dimer inhibitors from natural products

Midori A. Arai; Ayako Masada; Toshiyuki Ohtsuka; Ryoichiro Kageyama; Masami Ishibashi

doi:10.1016/j.bmcl.2009.07.146

The first Hes1 dimer inhibitors from natural products

Midori A. Arai, Ayako Masada, Toshiyuki Ohtsuka, Ryoichiro Kageyama, Masami Ishibashi

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

25 Citations (Scopus)

Abstract

In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.

Original language	English
Pages (from-to)	5778-5781
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	19
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2009.07.146
Publication status	Published - 2009 Oct 1
Externally published	Yes

Keywords

Hes1
High-throughput screening
Inhibitor
Neural stem cells
bHLH

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.2009.07.146

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title = "The first Hes1 dimer inhibitors from natural products",

abstract = "In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.",

keywords = "Hes1, High-throughput screening, Inhibitor, Neural stem cells, bHLH",

author = "Arai, {Midori A.} and Ayako Masada and Toshiyuki Ohtsuka and Ryoichiro Kageyama and Masami Ishibashi",

note = "Funding Information: This study was supported by a Grant-in-Aid for Young Scientists (A) (to M.A.A.) and in part by Grants-in-Aid for Scientific Research (B) (to M.I.) from Japan Society for the Promotion of Science (JSPS). M.A.A. also gratefully acknowledges Uehara Memorial Foundation for financial support. This work was also supported in part by the Hamaguchi Foundation for the Advancement of Biochemistry to M.A.A. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.bmcl.2009.07.146",

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AU - Arai, Midori A.

AU - Masada, Ayako

AU - Ohtsuka, Toshiyuki

AU - Kageyama, Ryoichiro

AU - Ishibashi, Masami

N1 - Funding Information: This study was supported by a Grant-in-Aid for Young Scientists (A) (to M.A.A.) and in part by Grants-in-Aid for Scientific Research (B) (to M.I.) from Japan Society for the Promotion of Science (JSPS). M.A.A. also gratefully acknowledges Uehara Memorial Foundation for financial support. This work was also supported in part by the Hamaguchi Foundation for the Advancement of Biochemistry to M.A.A. Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

PY - 2009/10/1

Y1 - 2009/10/1

N2 - In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.

AB - In the present study, we developed a high-throughput screening system for small molecule-inhibitors of the basic helix-loop-helix (bHLH) transcriptional repressor factor Hes1. Successful dimerization of Hes1 immobilized on a microplate and fluorophore (Cy3)-labelled Hes1 was confirmed. Using this system, several natural products were identified as the first Hes1 dimer inhibitors. Of these, two compounds which were isolated from myxomycetes (true slime molds) inhibited Hes1 from N box-dependent suppression of the gene expression in C3H10T1/2 cells.

KW - Hes1

KW - High-throughput screening

KW - Inhibitor

KW - Neural stem cells

KW - bHLH

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The first Hes1 dimer inhibitors from natural products

Abstract

Keywords

ASJC Scopus subject areas

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