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JK184

CAS No. : 315703-52-7

MCE 国际站：JK184

产品活性：JK184 是一种有效的 Hedgehog (Hh) 抑制剂，在哺乳动物细胞中，IC₅₀ 为 30 nM。

研究领域：Stem Cell/Wnt

作用靶点：Hedgehog

In Vitro: 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).

In Vivo: 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.

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