title: Hes1-Binding Compounds Isolated by Target Protein Oriented Natural Products Isolation (TPO-NAPI).
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Midori A
authors.identifier: 0000-0003-0254-9550
authors.initials: MA
authors.lastname: Arai
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Mitsuha
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Tanouchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ishikawa
authors.affiliation: Department of Pharmaceutical Chemistry, University of Dhaka , Dhaka1000, Bangladesh.
authors.forename: Firoj
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Pharmacy Discipline, Khulna University , Khulna 9208, Bangladesh.
authors.forename: Samir K
authors.initials: SK
authors.lastname: Sadhu
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Masami
authors.identifier: 0000-0002-2839-1045
authors.initials: M
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D001459:Bangladesh; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D002454:Cell Differentiation; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007769:Lactams / Q000737:chemistry*; D051379:Mice; D015394:Molecular Structure; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D035261:Plant Components, Aerial / Q000737:chemistry*; D000072056:Transcription Factor HES-1 / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001688:Biological Products; D018398:Homeodomain Proteins; D007769:Lactams; D000072056:Transcription Factor HES-1