Ligand-Based Discovery of a New Scaffold for Allosteric Modulation of the μ-Opioid Receptor

  title={Ligand-Based Discovery of a New Scaffold for Allosteric Modulation of the $\mu$-Opioid Receptor},
  author={Paola Bisignano and Neil T. Burford and Yi Shang and Brennica Marlow and Kathryn E. Livingston and Abigail M. Fenton and Kristin Rockwell and Lauren Budenholzer and John R. Traynor and Samuel W. Gerritz and Andrew Alt and Marta Filizola},
  journal={Journal of chemical information and modeling},
  volume={55 9},
With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators of the opioid receptors. In the past two years, the first chemotypes of positive or silent allosteric modulators (PAMs or SAMs, respectively) of μ- and δ-opioid receptor types have been reported in the literature. During a structure-guided lead optimization campaign with μ-PAMs BMS-986121 and BMS-986122 as starting compounds, we discovered a new chemotype that was… 

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