The first Hes1 dimer inhibitors from natural products.

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.

[1]  Y. Uehara,et al.  New cytotoxic bisindole alkaloids with protein tyrosine kinase inhibitory activity from a myxomycete Lycogala epidendrum. , 2005, Bioorganic & medicinal chemistry letters.

[2]  Y. Asakawa,et al.  Three novel dimethyl pyrroledicarboxylate, lycogarubins AC, from the myxomycetes lycogala epidendrum , 1994 .

[3]  T. Yamori,et al.  New bisindole alkaloids isolated from Myxomycetes Arcyria cinerea and Lycogala epidendrum. , 2005, Chemical & pharmaceutical bulletin.

[4]  S. Kato,et al.  High-throughput system for analyzing ligand-induced cofactor recruitment by vitamin D receptor. , 2007, Bioconjugate chemistry.

[5]  T. Ohtsuki,et al.  Secoiridoid components from Jasminum grandiflorum. , 2007, Phytochemistry.

[6]  H. Okano,et al.  Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum , 2006, The Journal of Neuroscience.

[7]  Peter G Schultz,et al.  A synthetic small molecule that induces neuronal differentiation of adult hippocampal neural progenitor cells. , 2006, Angewandte Chemie.

[8]  M. K. Lee,et al.  Lignan and neolignan glycosides fromUlmus davidiana var.japonica , 2001, Archives of pharmacal research.

[9]  Ryoichiro Kageyama,et al.  Roles of bHLH genes in neural stem cell differentiation. , 2005, Experimental cell research.

[10]  A. Michelucci,et al.  Dual bioactivity of resveratrol fatty alcohols: differentiation of neural stem cells and modulation of neuroinflammation. , 2007, Bioorganic & medicinal chemistry letters.

[11]  H. Sano,et al.  The structures of the novel protein kinase C inhibitors K-252a, b, c and d. , 1986, The Journal of antibiotics.

[12]  M. Hayashi,et al.  Dihydrolindbladiones, three new naphthoquinone pigments from a myxomycete Lindbladia tubulina. , 2003, Journal of natural products.

[13]  W. Steglich,et al.  Isolation and synthesis of 3,4-bis(indol-3-yl)pyrrole-2,5-dicarboxylic acid derivatives from the slime mould Lycogala epidendrum , 1994 .

[14]  M. Hayashi,et al.  Lindbladione and related naphthoquinone pigments from a myxomycete Lindbladia tubulina. , 2002, Chemical & pharmaceutical bulletin.

[15]  T. Ohtsuki,et al.  Lignan glycosides and flavonoids from Saraca asoca with antioxidant activity , 2007, Journal of Natural Medicines.

[16]  V. Vecchietti,et al.  Alkaloid and lignan constituents of Cinnamosma madagascariensis , 1979 .

[17]  J. de Barry,et al.  Panaxadiol glycosides that induce neuronal differentiation in neurosphere stem cells. , 2007, Journal of natural products.

[18]  Ryoichiro Kageyama,et al.  The Hes gene family: repressors and oscillators that orchestrate embryogenesis , 2007, Development.

[19]  Y. Tezuka,et al.  Hepatoprotective constituents of the seeds of Combretum quadrangulare. , 2000, Biological & pharmaceutical bulletin.

[20]  K. Nozaki,et al.  Adenovirus-Mediated Gene Transfer of Fibroblast Growth Factor-2 Increases BrdU-Positive Cells After Forebrain Ischemia in Gerbils , 2003, Stroke.

[21]  Y. Kojima,et al.  Studies on the Biosynthesis of Violacein, Part IV. A New Metabolite of Tryptophan, Chromopyrrolic Acid, Produced by Chromobacterium violaceum. , 1993 .

[22]  A. Benraiss,et al.  Adenoviral Brain-Derived Neurotrophic Factor Induces Both Neostriatal and Olfactory Neuronal Recruitment from Endogenous Progenitor Cells in the Adult Forebrain , 2001, The Journal of Neuroscience.