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MRT-83 is a potent antagonist of Smo, with an IC₅₀ in the nanomolar range. MRT-83 also blocks Hedgehog (Hh) signaling.

MRT-83 displays full antagonist properties with an IC₅₀ (~3 nM) for inhibiting ShhN (3 nM)-induced proliferation of rat GCPs. MRT-83 also blocks SAG (0.01 μM)-induced proliferation of GCPs (IC₅₀ ~6 nM). MRT-83 blocks BC binding to HEK-hSmo cells in a dose-dependent manner with an IC₅₀ of 4.6 nM. MRT-83 abrogates BC binding to cells expressing mouse Smo with an IC₅₀ of 14 nM, which is in good correlation with its IC₅₀ in the Shh-light2 and alkaline phosphatase assays.

Animals treated with ShhN in the presence of MRT-83 are as healthy as those of the other groups but up-regulation of Ptc transcription in the SVZ of these animals is no longer observed in agreement with a complete inhibition of ShhN-mediated effects (8.7±2.4 Ptc cells/section, n=9) and is not different from vehicle-mediated effects. MRT-83 but not MRT-36 antagonizes the up-regulation of Ptc transcription induced by ShhN in vivo in the SVZ of the LV.

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