scholarly journals Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity

2011 ◽  
Vol 21 (19) ◽  
pp. 5711-5714 ◽  
Author(s):  
Alan Fulp ◽  
Katherine Bortoff ◽  
Yanan Zhang ◽  
Herbert Seltzman ◽  
Rodney Snyder ◽  
...  
Keyword(s):  
Rational Design ◽  
Cannabinoid Receptor ◽  
Cannabinoid Receptor 1 ◽  
Cb1 Antagonists

scholarly journals Structure-Based Identification of Potent Natural Product Chemotypes as Cannabinoid Receptor 1 Inverse Agonists

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2630 ◽  
Author(s):  
Pankaj Pandey ◽  
Kuldeep Roy ◽  
Haining Liu ◽  
Guoyi Ma ◽  
Sara Pettaway ◽  
...  
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Binding Affinity ◽  
Cannabinoid Receptor ◽  
New Drugs ◽  
In Vitro Screening ◽  
Cannabinoid Receptor 1 ◽  
Cardiometabolic Disorders ◽  
Cb1 Antagonists

Natural products are an abundant source of potential drugs, and their diversity makes them a rich and viable prospective source of bioactive cannabinoid ligands. Cannabinoid receptor 1 (CB1) antagonists are clinically established and well documented as potential therapeutics for treating obesity, obesity-related cardiometabolic disorders, pain, and drug/substance abuse, but their associated CNS-mediated adverse effects hinder the development of potential new drugs and no such drug is currently on the market. This limitation amplifies the need for new agents with reduced or no CNS-mediated side effects. We are interested in the discovery of new natural product chemotypes as CB1 antagonists, which may serve as good starting points for further optimization towards the development of CB1 therapeutics. In search of new chemotypes as CB1 antagonists, we screened the in silico purchasable natural products subset of the ZINC12 database against our reported CB1 receptor model using the structure-based virtual screening (SBVS) approach. A total of 18 out of 192 top-scoring virtual hits, selected based on structural diversity and key protein–ligand interactions, were purchased and subjected to in vitro screening in competitive radioligand binding assays. The in vitro screening yielded seven compounds exhibiting >50% displacement at 10 μM concentration, and further binding affinity (Ki and IC50) and functional data revealed compound 16 as a potent and selective CB1 inverse agonist (Ki = 121 nM and EC50 = 128 nM) while three other compounds—2, 12, and 18—were potent but nonselective CB1 ligands with low micromolar binding affinity (Ki). In order to explore the structure–activity relationship for compound 16, we further purchased compounds with >80% similarity to compound 16, screened them for CB1 and CB2 activities, and found two potent compounds with sub-micromolar activities. Most importantly, these bioactive compounds represent structurally new natural product chemotypes in the area of cannabinoid research and could be considered for further structural optimization as CB1 ligands.

Mitochondrial energy metabolism is negatively regulated by cannabinoid receptor 1 in intact human epidermis

2020 ◽  
Vol 29 (7) ◽  
pp. 616-622 ◽  
Author(s):  
Attila Oláh ◽  
Majid Alam ◽  
Jérémy Chéret ◽  
Nikolett Gréta Kis ◽  
Zoltán Hegyi ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cannabinoid Receptor ◽  
Human Epidermis ◽  
Cannabinoid Receptor 1 ◽  
Mitochondrial Energy Metabolism

scholarly journals Audiograms, gap detection thresholds, and frequency difference limens in cannabinoid receptor 1 knockout mice

2016 ◽  
Vol 332 ◽  
pp. 217-222 ◽  
Author(s):  
Katrina L. Toal ◽  
Kelly E. Radziwon ◽  
David P. Holfoth ◽  
Matthew A. Xu-Friedman ◽  
Micheal L. Dent
Keyword(s):  
Knockout Mice ◽  
Cannabinoid Receptor ◽  
Frequency Difference ◽  
Gap Detection ◽  
Cannabinoid Receptor 1 ◽  
Detection Thresholds

Effects on Food Intake and Blood Lipids of Cannabinoid Receptor 1 Antagonist Treatment in Lean Rats

Obesity ◽  
2008 ◽  
Vol 16 (11) ◽  
pp. 2451-2455 ◽  
Author(s):  
Marianne F. Bennetzen ◽  
Maria P. Nielsen ◽  
Bjørn Richelsen ◽  
Steen B. Pedersen
Keyword(s):  
Food Intake ◽  
Blood Lipids ◽  
Cannabinoid Receptor ◽  
Cannabinoid Receptor 1
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