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Biological Activity
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Description
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LY2940680 binds to the Smo receptor and potently inhibits Hh signaling. |
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Targets
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Smo |
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IC50 |
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In Vitro
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LY2940680 inhibits cancer growth in cell lines containing a mutation in the gene encoding Smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib. [1] |
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In Vivo
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LY2940680 has excellent pharmacokinetic properties in rodent and non-rodent species. LY2940680 administrated orally treats Ptch+/- p53-/- transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. LY2940680 reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and LY2940680 induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. LY2940680 inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity. [2] |
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Clinical Trials
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LY2940680 is currently being tested in phase 1 trials for people with a range of solid tumors. |
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Features
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Combination Therapy
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Description
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LY2940680 inhibits the functional activity of resistant Smo mutant (D473H) produced by treatment with GDC-0449 (a Smo antagonist). sup>[2] |
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