Benjamin F. Cravatt

TL;DR: In this article, a functional screening strategy performed with a focused library of candidate electrophilic PROTACs to discover bifunctional compounds that degrade proteins in human cells by covalently engaging E3 ligases was described.

TL;DR: It is shown that pharmacological activation of CB1Rs dampens the tumor necrosis factor α (TNFα)-mediated potentiation of striatal spontaneous glutamate-mediated excitatory postsynaptic currents (EPSCs), which is believed to cogently contribute to the inflammation-induced neurodegenerative damage observed in EAE mice.

TL;DR: The development of potent and selective inhibitors of the biosynthesis of the endocannabinoid 2‐arachidonoylglycerol (2‐AG) via DAG lipases (DAGL) α and β is just starting to be considered as a novel and promising source of pharmaceuticals for the treatment of disorders that might benefit from a reduction in endOCannabinoid tone, such as hyperphagia in obese subjects.

TL;DR: The results indicate that AIG1 and ADTRP are founding members of an evolutionarily conserved class of transmembrane threonine hydrolases involved in bioactive lipid metabolism and demonstrate how chemical proteomics can excavate potential cases of convergent/parallel protein evolution that defy conventional sequence- and structure-based predictions.

TL;DR: It is suggested that inhibition of endocannabinoid degradative enzymes represents a promising therapeutic approach to decrease effective doses of opioids needed for clinical pain control, and may also possess therapeutic potential to reduce opioid abuse.