JK184 --- Hedgehog Antagonist

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 (IC50 ~ 3 - 21 nM), and inhibits the growth of two xenografted tumors in mice in vivo.

Product information

CAS Number: 315703-52-7

Molecular Weight: 350.44

Formula: C19H18N4OS

Chemical Name: N-(4-Ethoxyphenyl)-4-(2-methylimidazo[1,2-a]pyridin-3-yl)-2-thiazolamine

Smiles: CC1N=C2C=CC=CN2C=1C1=CSC(NC2=CC=C(C=C2)OCC)=N1

InChiKey: ROYXIPOUVGDTAO-UHFFFAOYSA-N

InChi: InChI=1S/C19H18N4OS/c1-3-24-15-9-7-14(8-10-15)21-19-22-16(12-25-19)18-13(2)20-17-6-4-5-11-23(17)18/h4-12H,3H2,1-2H3,(H,21,22)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

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.

References:

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.

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

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