JK184 (5 mg/kg, injected intravenously) demonstrates significant anti-proliferative effects in subcutaneous Panc-1 and BxPC-3 tumor models, positioning it as a promising candidate for targeting Hh signaling in anticancer therapy. However, JK184 suffers from limitations in its pharmacokinetic profile and bioavailability^[1].

JK184 is formulated to antagonize Hedgehog (Hh) signaling by impeding glioma (Gli)-dependent transcriptional activity in a dose-dependent manner. It significantly inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) with an IC50 of 6.3 μg/mL after three days of incubation. To assess the anti-tumor effect of JK184, an MTT assay is conducted in Panc-1 and BxPC-3 cells after treatment with specified compound concentrations, revealing a half-maximal inhibitory concentration (IC50) of JK184 (23.7 ng/mL in Panc-1 and 34.3 ng/mL in BxPC-3)^[1].

Claudin-low cell lines exhibit higher sensitivity to JK184 treatment compared to MCF10a, MTSV1-7, or HMLE-shGFP and HMLE-pBP cells. JK184 induces 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 increases the proportion of HMLE-shEcad cells staining positive for Annexin-V but negative for propidium iodide (PI) (P<0.0001)^[2].