Cover Picture: Synthesis and Evaluation of Osteogenic Oxysterols as Hedgehog Pathway Activators (ChemMedChem 7/2016)

Abstract

The front cover picture shows how the stereochemical orientation of the C-21 methyl group in the oxysterol (OHC) scaffold can determine whether the OHC serves as an agonist of the hedgehog (Hh) signaling pathway (hedgehog image by Marina Maslennikova, iStockphoto). The natural configuration of the C-21 methyl is R, which is shown here in the structure of natural 23(S)-hydroxycholesterol (4, right), a potent, synthetic agonist of Hh signaling with the ability to promote osteogenic differentiation. Inversion of the C-21 methyl to the S configuration (16, left) completely abolished its ability to activate Hh signaling. These results provide essential structural insight for the future development of small molecule OHCs as Hh pathway agonists. More information can be found in the Full Paper by M. Kyle Hadden et al. on page 679 in Issue 7, 2016 (DOI: 10.1002/cmdc.201500550).