John Frazer

TL;DR: This work focuses on the design and implementation of high-throughput GPCR functional assays that allow the cost-effective screening of large compound libraries to identify novel drug candidates.

TL;DR: It is found that small molecule ligands modulate numerous G protein-dependent and independent pathways through MAS1, including Gq and Gi pathways, GTPγS binding, β-arrestin recruitment, Erk1/2 and Akt phosphorylation, arachidonic acid release, and receptor internalization, and in dynamic mass redistribution (DMR) assays that provide a pathway-agnostic readout of cellular responses, small molecule agonists produced robust responses.

TL;DR: This study provides a mechanistic basis for the long durations of action in vivo and wash-resistant effects in ex vivo tissue models often observed for ergots and indicates that persistent signaling originated from internalized or sequestered receptors.

TL;DR: A new family of Histamine H(3) receptor antagonists (5a-t) has been prepared based on the structure of the natural product Conessine, a known H(2) receptor antagonist, which exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H( 3) receptor in an in-vivo pharmacological model.

TL;DR: A series of 5-HT(2A) inverse-agonists that when dosed in rats, both consolidate the stages of NREM sleep, resulting in fewer awakenings, and increase a physiological measure of sleep intensity are described.