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JK184 is a potent and cell-permeable inhibitor of hedgehog (Hh) signaling downstream of Smo, identified by a cell-based Hh pathway reporter screening. JK184 was found to inhibit Adh7 (IC₅₀?~210 nM), the class IV alcohol dehydrogenase as well as act as a microtubule depolymerizing agent in vitro. JK184 inhibits Hh agonit-induced Gli transcriptional activity (IC₅₀?~30 nM) as well as Gli1 and Ptc1 mRNA expression in a dose-dependent manner in 10T1/2 cells. It shows antiproliferative activity in a range of cancer cell lines (IC_50?~ 3 - 21 nM), and inhibits the growth of two xenografted tumors in mice in vivo.

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How to Use:?

• In vitro:?JK184 was suggested to use at 1-5 μM concentration in vitro and in the cellular assays.
• In vivo:?JK184 was dosed orally 0.2 mg/mouse once per day. ?

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Reference:

• 1. Lee J, et al. A small-molecule antagonist of the hedgehog signaling pathway. (2007)?Chembiochem????? 8(16):1916-9.
• 2. Cupido T, et al. The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling. (2009)Angew Chem Int Ed Engl.????? 48(13):2321-4.

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Products are for research use only. Not for human use.