JK184 是 Hedgehog 抑制剂，在哺乳动物细胞中的IC50值为 30 nM。

JK184 is a potent Hedgehog (Hh) pathway inhibitor.

JK184 is designed to antagonize Hh signaling by inhibiting glioma (Gli)-dependent transcriptional activity in a dose dependent manner. JK184 significantly inhibits the proliferation of HUVECs with IC50 of 6.3 μg/mL after three days incubation. MTT assay is conducted in Panc-1 and BxPC-3 cells after administration with indicated concentrations of compounds, half maximal inhibitory concentration (IC50) of JK184 (23.7 ng/mL in anc-1 and 34.3 ng/mL in BxPC-3) to evaluate anti-tumor effect of JK184[1]. Claudin-low cell lines are more sensitive to JK184 treatment than are MCF10a, MTSV1-7, or HMLE-shGFP and HMLE-pBP cells, and JK184 induced a dose-dependent decrease in glioma-associated oncogene homolog 1 (GLI1) transcript and protein levels in these cells. Treatment with the IC50 dose of JK184 enhances the proportion of HMLE-shEcad cells that stained with Annexin-V, but are negative for propidium iodide (PI) (P<0.0001, t test)[2].

JK184 (5 mg/kg, injected intravenously) exhibits good anti-proliferative activity in subcutaneous Panc-1 and BxPC-3 tumor models, and is a good candidate as antitumor drug targeted Hh signaling. Histological analysis showed that JK184 improved anti-tumor activity by inducing more apoptosis, decreasing microvessel density, and reducing expression of CD31, Ki67, and VEGF in tumor tissues. However, JK184 has a poor pharmacokinetic profile and bioavailability[1].

JK184 is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. The Shh-LIGHT2 cells are seeded in 96-well plates and grown to confluency. The Shh-LIGHT2 cells are treated with various concentrations of JK184 micelles or free JK184 or micelles in DMEM containing 0.5% CS, 0.1 mg/mL streptomycin, 100 U/mL penicillin, 5% Shh-N conditioned medium obtained from Shh-N-producing HEK293 cells. The treated cells are cultured further for 60 h, and firefly and Renilla luciferase activities are measured using a dual luciferase kit. Proliferation assay or apoptosis evaluation of HUVECs is measured using MTT method or FCM analysis, respectively. HUVECs are treated with a series concentration of free JK184, JK184 micelles, or blank MPEG-PCL micelles for 48 h, respectively. The mean percentage of cell inhibition or apoptosis is calculated[1].

315703-52-7

C19H18N4OS

350.44

DMSO:10 mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years