In this work, we tried to find a new scaffold for a CB1 receptor antagonist using virtual screening. We first analyzed structural features for the known cannabinoid-1 receptor antagonists and, then, we built pharmacophore models using the HipHop concept and carried out a docking study based on our homology CB1 receptor 3D structure. The most active compound, including thiazole-4-one moiety, showed an activity value of 125 nM IC(50), with a good PK profile.
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http://dx.doi.org/10.1016/j.bmcl.2010.07.018 | DOI Listing |
J Dairy Sci
January 2025
Department of Ruminant Science, Institute of Animal Sciences, ARO Volcani Institute, Israel; Department of Animal Science, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
The endocannabinoid system (ECS) is involved in the regulation of energy metabolism, immune function and reproduction in mammals. The ECS is consisted of the endocannabinoid (eCB) ligands, enzymes, and cannabinoid receptors. In mammals, the cannabinoid-1 receptor (CB1/CNR1) is expressed in the central nervous system and in peripheral tissues; and its activation increases anabolic processes.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Tetrahydrocannabinol (THC) is the principal psychoactive compound derived from the cannabis plant Cannabis sativa and approved for emetic conditions, appetite stimulation and sleep apnea relief. THC's psychoactive actions are mediated primarily by the cannabinoid receptor CB. Here, we determine the cryo-EM structure of HU210, a THC analog and widely used tool compound, bound to CB and its primary transducer, G.
View Article and Find Full Text PDFInt J Pharm
December 2024
Hacettepe University, Faculty of Medicine, Department of Histology and Embryology, 06100, Sıhhiye, Ankara, Turkey; METU MEMS Center, 06530, Ankara, Turkey. Electronic address:
Rapid progressing non-small cell lung adenocarcinoma (NSCLC) decreases treatment success. Cannabinoids emerge as drug candidates for NSCLC due to their anti-tumoral capabilities. We previously reported the controlled release of Arachidonylcyclopropylamide (ACPA) selectively targeting cannabinoid 1 (CB1) receptor in NSCLC cells in vitro.
View Article and Find Full Text PDFProteins
November 2024
Department of Chemistry, University of Southern California, Los Angeles, California, USA.
G-protein-coupled receptors (GPCRs) constitute one of the most prominent families of integral membrane receptor proteins that mediate most transmembrane signaling processes. Malfunction of these signal transduction processes is one of the underlying causes of many human pathologies (Parkinson's, Huntington's, heart diseases, etc), provoking that GPCRs are the largest family of druggable proteins. However, these receptors have been targeted traditionally by orthosteric ligands, which usually causes side effects due to the simultaneous targeting of homologous receptor subtypes.
View Article and Find Full Text PDFJ Cardiopulm Rehabil Prev
January 2025
Author Affiliations: Marshfield Clinic Research Institute, Marshfield, Wisconsin (Dr Rezkalla); Cardiovascular Research Institute, Huntington Medical Research Institutes, Pasadena, California (Dr Kloner); and Cardiovascular Division, Dept. of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, California (Dr Kloner).
Objective: Cannabinoids exert their effects on body tissues via cannabinoid 1 (CB 1 ) and cannabinoid 2 (CB 2 ) receptors. Receptors are present in brain, myocardium, vascular endothelium, platelets, and adipose tissues. Under normal physiologic conditions, endocannabinoid effects are minimal.
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