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

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

  • Chem Sci. 2016 Feb 1;7(2):1514-1520. doi: 10.1039/c5sc03540f.
Midori A Arai 1,  Naoki Ishikawa 1,  Mitsuha Tanaka 1,  Kenji Uemura 1,  Noriko Sugimitsu 1,  Akiko Suganami 2,  Yutaka Tamura 2,  Takashi Koyano 3,  Thaworn Kowithayakorn 4,  Masami Ishibashi 1
Affiliations

Affiliations

  • 1 Graduate School of Pharmaceutical Sciences , Chiba University , 1-8-1 Inohana, Chuo-ku , Chiba 260-8675 , Japan . Email: midori_arai@chiba-u.jp ; Email: mish@chiba-u.jp.
  • 2 Graduate School of Medicine , Chiba University , 1-8-1 Inohana, Chuo-ku , Chiba 260-8670 , Japan.
  • 3 Temko Corporation , 4-27-4 Honcho, Nakano , Tokyo 164-0012 , Japan.
  • 4 Faculty of Agriculture , Khon Kaen University , Khon Kaen 40002 , Thailand.
PMID: 29899896 DOI: 10.1039/c5sc03540f
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.

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