HhAntag 

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

450.92

Solid

C₂₄H₂₃ClN₄O₃

496794-70-8

O=C(NC1=CC=C(Cl)C(C2=NC3=CC=C(N(C)C)C=C3N2)=C1)C4=CC(OC)=CC(OC)=C4

Room temperature in continental US; may vary elsewhere.

• [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.  [Content Brief]