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Overview
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Background
IC50: from ~2 μM to >30 μMHhAntag is a Hedgehog signaling antagonist. Ligand-dependent activation of the Hedgehog (Hh) signaling pathway has been associated with tumorigenesis in a number of human tissues.In vitro: HhAntag has been evaluated for its effect on Hh pathway across a large panel of cancer cell lines. HhAntag demonstrated to be around 10-times more potent than cyclopamine at inhibiting the activity of Hh pathway. A range of cellular sensitivities to HhAntag was observed with IC50 values for growth inhibition ranging from ~2 μM to >30 μM. In contrast to previous reports, no tissue specificity of in vitro sensitivity to HhAntag was observed [1]. In vivo: Oral administration of HhAntag to mice with primary human xenografts resulted in significant growth delay in both pancreatic and colon adenocarcinoma models, with average tumour growth inhibitions of 29% and 48%, respectively. Moreover, the HhAntag doses required to inhibit the tumor growth were similar to the doses required to fully inhibit endogenous Hh target genes in tumour stroma or in surrogate normal tissues, indicating that such growth inhibition was a specific consequence of Hh inhibition [1]. Clinical trial: N/A
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