20(S)-Hydroxycholesterol (20α-Hydroxycholesterol) is an allosteric activator that selectively targets the Smoothened ( Smo ) of the Hedgehog pathway with an EC 50 of ~30 μM ( Hedgehog ). 20(S)-Hydroxycholesterol binds to the extracellular cysteine-rich domain (CRD) of Smo in a stereoselective manner, activating downstream Gli transcription factors (without inducing transcription of receptor genes in the Wnt pathway). 20(S)-Hydroxycholesterol enhances osteogenic differentiation of bone marrow stromal cells and synergistically activates the Raf/MEK/ERK pathway with Simvastatin ( HY-17502 ) to promote bone regeneration. 20(S)-Hydroxycholesterol can be used to study the mechanisms of developmental biology, oncology, bone, and angiogenesis.
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