Hes1 inhibitor isolated by target protein oriented natural products isolation (TPO-NAPI) of differentiation activators of neural stem cells

Midori A. Arai, Naoki Ishikawa, Mitsuha Tanaka, Kenji Uemura, Noriko Sugimitsu, Akiko Suganami, Yutaka Tamura, Takashi Koyano, Thaworn Kowithayakorn, Masami Ishibashi

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11 Citations (Scopus)

Abstract

The Hes1 dimer inhibitor, agalloside (2), which can accelerate the differentiation of neural stem cells is described. Six natural products, including one new natural product, which bind to Hes1 were rapidly isolated by a developed "target protein oriented natural products isolation" (TPO-NAPI) method using Hes1-immobilized beads. Of the six compounds, 2 inhibited Hes1 dimer formation at both the protein- and cellular level. Neural stem cells treated with 2 differentiated to neurons with longer neurites than cells treated with varproic acid or retinoic acid. Moreover, 2 exhibited specificity for neurons. This promotion of differentiation was supported by an increase in the mRNA expression of the proneural genes, Mash1 and Ngn2, which were inhibited by Hes1.

Original languageEnglish
Pages (from-to)1514-1520
Number of pages7
JournalChemical Science
Volume7
Issue number2
DOIs
Publication statusPublished - 2016

ASJC Scopus subject areas

  • Chemistry(all)

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    Arai, M. A., Ishikawa, N., Tanaka, M., Uemura, K., Sugimitsu, N., Suganami, A., Tamura, Y., Koyano, T., Kowithayakorn, T., & Ishibashi, M. (2016). Hes1 inhibitor isolated by target protein oriented natural products isolation (TPO-NAPI) of differentiation activators of neural stem cells. Chemical Science, 7(2), 1514-1520. https://doi.org/10.1039/c5sc03540f