JK 184 [Hedgehog Inhibitor]

JK184 is a highly potent hedgehog (Hh) pathway inhibitor with IC50 of 30 nM in mammalian cells.

N-(4-Ethoxyphenyl)-4-(2-methylimida zo[1,2-a]pyridin-3-yl)-2-thiazolamine

Inhibitor

Neurological Disorders

JK184 is designed to antagonize Hh signaling by inhibiting glioma (Gli)-dependent transcription activity in a dose-dependent manner. After three days of incubation, JK184 significantly inhibited the proliferation of HUVEC with IC50 of 6.3 μg/mL. In order to evaluate the antitumor effect of JK184, MTT analysis was performed in Panc-1 and BxPC-3 cells after administration of the specified concentration of compound, and the half-maximum inhibitory concentration (IC50) of JK184 (23.7 ng in anc-1 and 34.3 mL) ng / mL (in BxPC-3) [1]. Claudine low cell line is more sensitive to JK184 treatment than MCF10a, MTSV1-7 or HMLE-shGFP and HMLE-pBP cells, and JK184 induces glioma-related oncogene homolog 1 (GLI1) transcript and protein dose Dependence reduces the levels in these cells. Treatment with IC50 dose of JK184 can increase the proportion of HMLE-shEcad cells stained with Annexin-V but negative for propidium iodide (PI) (P<0.0001, t test) [2].

[1]. Zhang N, et al. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway. Nanoscale. 2015 Feb 14;7(6):2609-24.

[2]. Colavito SA, et al. Significance of glioma-associated oncogene homolog 1 (GLI1) expression in claudin-low breast cancer and crosstalk with the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway. Breast Cancer Res. 2014 Sep 25;16(5):444.

JK184 (5 mg/kg, intravenous injection) shows good antiproliferative activity in the subcutaneous Panc-1 and BxPC-3 tumor models, and is a good candidate for anti-tumor drugs that target Hh signaling. However, JK184 has poor pharmacokinetics and bioavailability [1].

[1]. Zhang N, et al. Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway. Nanoscale. 2015 Feb 14;7(6):2609-24.

350.44

Powder

C19H18N4OS

Synthetic

CC2=C(C3=CSC(NC4=CC=C(OCC)C=C4)=N3)N1C=CC=CC1=N2

Soluble in DMSO (100mM) or ethanol (25mM)

30 nM

315703-52-7

1069686

>99%

Store at +4°C

Room Temperature

For obtaining a higher solubility, please warm the tube at 37 °C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -40°C for several months.

For research use only

Hedgehog

Hedgehog

Hedgehog

Hh

6469(Human)

Q15465(Human)