JK184

＞98%

Store at -20℃ for one year（Powder）；Store at 2-4℃ for two weeks；Store at -20℃ for six months after dissolution.

Solid

JK 184；JK-184；Hh Signaling Antagonist VII

off-white to light brown powder

~1.3 g/cm³ (Predicted)

n²⁰_D 1.68 (Predicted)

enzymatic activity of Adh7: IC₅₀ = 210 nM; Hg-Ag-induced Gli-transcription activity : IC₅₀ = 30 nM; sonic hedgehog induced Gli transcription: IC₅₀ = 30 nM

DMSO : ≥ 50 mg/mL (142.68 mM)

1069686

Hedgehog

JK184 is designed to antagonize Hh signaling by inhibiting glioma (Gli)-dependent transcriptional activity in a dose dependent manner. JK184 significantly inhibitts proliferation of HUVECs with IC50 of 6.3 μg/mL after three days incubation. To evaluate anti-tumor effect of JK184, 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). 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).

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. However, JK184 has a poor pharmacokinetic profile and bioavailability.