Targeting Cannabinoid Receptors: Current Status and Prospects of Natural Products.
Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used. Recently, more detailed structural information for cannabinoid receptors was revealed thanks to the powerfulness of cryo-electron microscopy, which now can accelerate structure-based drug discovery. At the same time, novel peptide-type cannabinoids from animal sources have arrived at the scene, with their potential in vivo therapeutic effects in relation to cannabinoid receptors. From a natural products perspective, it is expected that more novel cannabinoids will be discovered and forecasted as promising drug leads from diverse natural sources and species, such as animal venoms which constitute a true pharmacopeia of toxins modulating diverse targets, including voltage- and ligand-gated ion channels, G protein-coupled receptors such as CB1 and CB2, with astonishing affinity and selectivity. Therefore, it is believed that discovering novel cannabinoids starting from studying the biodiversity of the species living on planet earth is an uncharted territory.
['An|Dongchen|D|', 'Peigneur|Steve|S|0000-0003-0504-5702', 'Hendrickx|Louise Antonia|LA|0000-0002-9317-7862', 'Tytgat|Jan|J|']
D000818:Animals D001688:Biological Products D063386:Cannabinoid Receptor Agonists D063387:Cannabinoid Receptor Antagonists D002186:Cannabinoids D055808:Drug Discovery D006801:Humans D062105:Molecular Docking Simulation D010455:Peptides D043882:Receptors, Cannabinoid
synthetic cannabinoids animal venoms cannabinoid receptor type 1 (CB1) and type 2 (CB2) phytocannabinoids structural analysis