JK184

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

JK184 是刺猬 (Hh) 信号通路的拮抗剂和 Gli 抑制剂。

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.

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.

JK-184 | JK 184

Wnt/Notch/Hedgehog

Gli

Hedgehog

Cancer

——

315703-52-7

350.44

C19H18N4OS

>98% (HPLC)

10 mM in DMSO

CC1=C(C2=CSC(NC3=CC=C(OCC)C=C3)=N2)N4C=CC=CC4=N1

2-Thiazolamine, N-(4-ethoxyphenyl)-4-(2-methylimidazo[1,2-a]pyridin-3-yl)-

(-20℃)

With Ice Pack

≥ 2 years