JK 184

• CAT Number: I003124
• CAS Number: 315703-52-7
• Molecular Formula: C₁₉H₁₈N₄OS
• Molecular Weight: 350.44
• Purity: ≥95%
• Target: Hedgehog
• Solubility: 10 mM in DMSO
• Storage: Store at +4C
• InChI: InChI=1S/C19H18N4OS/c1-3-24-15-9-7-14(8-10-15)21-19-22-16(12-25-19)18-13(2)20-17-6-4-5-11-23(17)18/h4-12H,3H2,1-2H3,(H,21,22)
• InChIKey: ROYXIPOUVGDTAO-UHFFFAOYSA-N
• SMILES: CCOC1=CC=C(C=C1)NC2=NC(=CS2)C3=C(N=C4N3C=CC=C4)C

JK184 is a potent Hedgehog (Hh) pathway inhibitor with IC50 of 30 nM in mammalian cells.IC50 & Target: 30 nM (Hedgehog)[1]InVitro: 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)[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].InVivo: 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[1].

Reference

1:Biodegradable polymeric micelles encapsulated JK184 suppress tumor growth through inhibiting Hedgehog signaling pathway. Zhang N, Liu S, Wang N, Deng S, Song L, Wu Q, Liu L, Su W, Wei Y, Xie Y, Gong C.Nanoscale. 2015 Feb 14;7(6):2609-24. doi: 10.1039/c4nr06300g. PMID: 25581613 2:The imidazopyridine derivative JK184 reveals dual roles for microtubules in Hedgehog signaling. Cupido T, Rack PG, Firestone AJ, Hyman JM, Han K, Sinha S, Ocasio CA, Chen JK.Angew Chem Int Ed Engl. 2009;48(13):2321-4. doi: 10.1002/anie.200805666. PMID: 19222062