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.
Arai
Midori A
MA
Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan. marai@p.chiba-u.ac.jp
Masada
Ayako
A
Ohtsuka
Toshiyuki
T
Kageyama
Ryoichiro
R
Ishibashi
Masami
M
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry*; D002460:Cell Line; D003998:Dicarboxylic Acids / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D019281:Dimerization; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D055767:Immobilized Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009235:Myxomycetes / Q000737:chemistry; D009285:Naphthoquinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D001688:Biological Products; D003998:Dicarboxylic Acids; D018398:Homeodomain Proteins; D055767:Immobilized Proteins; D009285:Naphthoquinones; D011758:Pyrroles; D011994:Recombinant Proteins; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C545114:lindbladione; C545115:lycogaric acid A