HhAntag

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

HhAntag 是 GLI1 介导的转录的小分子抑制剂，GLI1 介导的转录是 Hedgehog (Hh) 通路的重要下游元件，具有抗肿瘤活性。

HhAntag is a GLI1-mediated transcription inhibitor. It acts as an inhibitor of the Shh pathway.

HhAntag (2-30 μM; 72?hours) demonstrates to be?10-times more potent than the natural product SMO antagonist, cyclopamine, at inhibiting Hh pathway activity and it inhibits Hh signalling pathway sensitivitive cells with IC50 values ranging from 2?μM to >30?μM.HhAntag inhibits AsPC-1, BXPC-3, CFPAC, HPAC, HPAF-II, KP4, Panc 03.27, PA-TU-8902, PSN-1, SU.86.86 cells with IC50 values of 30 μM, 5.4 μM, 5.8 μM, 2.7 μM, 6.2 μM,10.3 μM, 2.5 μM, 2.9 μM, 5.8 μM and 2.7 μM, respectively.HhAntag (100 nM) is needed to completely inhibit Hh signalling in a Hh-responsive human mesenchymal cell line (HEPM) expressing a?GLI?luciferase reporter construct (HEPM-rep), the IC50?of 5?nM 400-times lower than that required to inhibit cell growth by 50% in the most sensitive cancer cell line (1.9?μM).

HhAntag (oral administraion; 75 mg/kg or 100 mg/kg; twice daily; 25 days) results in significant growth delay in HT55 and HT-29 colorectal cell line xenografts models, with average tumour growth inhibitions of 29% and 48%, respectively. Whereas HhAntag had no effect on the growth of DLD-1 xenografts. Animal Model:Primary human xenografts?in?female CD1 nu/nu mice of 6–8?weeks (DLD-1, HT55 and HT-29 cells)Dosage:75 mg/kg or 100 mg/kg Administration:Oral administraion; twice daily; 25 days Result:Resulted in growth delay of HT55 and HT-29 xenografts, but had no effects on DLD-1 xenografts.

HhAntag | Hh-Antag | Hh Antag

Membrane Transporter/Ion Channel

TRP/TRPV Channel

Gli

Cancer

——

496794-70-8

450.92

C24H23ClN4O3

>98% (HPLC)

DMSO : ≥ 100 mg/mL. 221.77 mM; H2O : < 0.1 mg/mL

C(=O)(c1cc(cc(c1)OC)OC)Nc1cc(c(cc1)Cl)c1nc2c([nH]1)cc(cc2)N(C)C

N-[4-Chloro-3-[6-(dimethylamino)-1H-benzimidazol-2-yl]phenyl]-3,5-dimethoxybenzamide

(-20℃)

With Ice Pack

≥ 2 years