JK184

SKU: orb1225327

Description

JK184 is an ntagonist of the hedgehog (Hh) signaling pathway and Gli inhibitor; inhibits GLI1 mRNA expression and decreases the number of colonies formed in TN-IBC (SUM149) and TNBC (MDA-MB-231 and SUM159) cell lines; significantly down-regulates GLI1 targets that regulate cell cycle (cyclin D and E) and apoptosis (Bcl2); JK184 is a potent inhibitor of microtubule assembly and that microtubule-depolymerizing agents can either negatively or positively regulate the Gli family of transcription factors, dependending on the mechanism by which the pathway is activated.

Key Properties

• CAS Number: 315703-52-7
• MW: 350.44
• Purity: >98% (HPLC)
• Formula: C₁₉H₁₈N₄OS
• SMILES: CC1=C(C2=CSC(NC3=CC=C(OCC)C=C3)=N2)N4C=CC=CC4=N1
• Target: Gli
• Solubility: 10 mM in DMSO

Bioactivity

• 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.
• 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).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

JK-184 | JK 184

Quick Database Links

Gene Symbol

Gli