HhAntag

• CAT Number: I003742
• CAS Number: 496794-70-8
• Molecular Formula: C24H23ClN4O3
• Molecular Weight: 450.92
• Purity: ≥95%
• Synonyms: N-[4-chloro-3-[6-(dimethylamino)-1H-benzimidazol-2-yl]phenyl]-3,5-dimethoxybenzamide
• InChI: InChI=1S/C24H23ClN4O3/c1-29(2)16-6-8-21-22(12-16)28-23(27-21)19-11-15(5-7-20(19)25)26-24(30)14-9-17(31-3)13-18(10-14)32-4/h5-13H,1-4H3,(H,26,30)(H,27,28)
• InChIKey: UBHJFPVTEATUFS-UHFFFAOYSA-N
• SMILES: CN(C)C1=CC2=C(C=C1)N=C(N2)C3=C(C=CC(=C3)NC(=O)C4=CC(=CC(=C4)OC)OC)Cl

HhAntag is a specific, potent and orally active small molecule SMO antagonist of the Hh pathway[1].
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[1].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[1].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)[1].
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[1].

Reference

[1]. Neeraj Mahindroo, et al. Amide conjugates of ketoprofen and indole as inhibitors of Gli1-mediated transcription in the Hedgehog pathway. Bioorg Med Chem. 2010 Jul 1;18(13):4801-11.
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