Hes1-Binding Compounds Isolated by Target Protein Oriented Natural Products Isolation (TPO-NAPI)

作者：Arai Midori A^*; Tanaka Mitsuha; Tanouchi Kana; Ishikawa Naoki; Ahmed Firoj; Sadhu Samir K; Ishibashi Masami^*

来源：Journal of Natural Products, 2017, 80(2): 538-543.

DOI：10.1021/acs.jnatprod.6b01072

Hairy and enhancer of split 1 (Hes1) is a transcription factor that acts in neural stem cells to inhibit differentiation. We recently developed target protein oriented natural products isolation (TPO-NAPI) using Hes1-immobilized beads to identify activators of neural stem cells. Isomicromonolactam (1), staurosporin (2), and linarin (3) were isolated as Hes1-binding compounds using the TPO-NAPI method. Of these, compound 1 enhanced neural stem cell differentiation. Using truncated Hes1 proteins, the binding region of Hes1 for 1 was estimated to be in the C-terminal half that includes a TLE/Grg binding site. The differentiation-promoting activity of inohanamine (4) is also reported.

• 出版日期2017-2