N-(4-Ethoxyphenyl)-4-(2-methylimidazo[1,2-a]pyridin-3-yl)-2-thiazolamine (JK 184)
• Hedgehog signaling inhibitor that prevents Gli-dependent transcriptional activity (IC50 = 30 nM). Exhibits antiproliferative activity in a range of cancer cell lines (GI50 = 3 - 21 nM) and in human xenografts in vivo. Inhibits alcohol dehydrogenase 7 (Adh7) (IC50 = 210 nM) and acts as a microtubule depolymerizing agent in vitro
OTAVAchemicals Catalogue Number: 7211760148
CAS Registry Number: 315703-52-7
Purity: 95%+ (HPLC)
Ref. 1: Schultz et al. A small-molecule antagonist of the Hedgehog signaling pathway. ChemBioChem (2007), 8, 1916-1919
Abstract: JK184 was identified as an antagonist of Hedgehog signaling through a cell-based screen of chemical libraries. Results from biochemical and cellular experiments suggest that JK184 functions by inhibiting class IV alcohol dehydrogenase. This molecule should serve as a useful tool for studying Hedgehog signaling.
Ref. 2: Chen et al. The imidazopyridine derivative JK184 reveals dual roles for microtubules in hedgehog signaling. Angewandte Chemie, International Edition (2009), 48, 2321-2324
Abstract: Eradicating hedgehogs: The title molecule has been previously identified as a potent inhibitor of the Hedgehog signaling pathway, which gives embryonic cells information needed to develop properly. This molecule is shown to modulate Hedgehog target gene expression by depolymerizing microtubules, thus revealing dual roles of the cytoskeleton in pathway regulation.