This talk will focus on emerging trends in signal bias amongst different series of allosteric modulators of both muscarinic acetylcholine receptors and metabatropic glutamate receptors by stabilizing unique activated conformations of the GPCR.   Of particular note, biased signalling enabled an mGlu<sub>5</sub> PAM to advance into IND-enabling studies by virtue of bias away from direct activation of NMDA receptors, and subtle structural variations modulate calcium, beta-arrestin and p-ERK signaling within a series of M<sub>1</sub> PAMs.   SAR trends, the practicality of driving a program based on signal bias and opprotunities for CNS drug discovery will be discussed as well.

Biased signaling with allosteric modulators of GPCRs

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.