生物活性

• 靶点	Cannabinoid Receptor 1 IC50:13.6nM

• 描述Rimonabant is a first selective oral antagonist of CB1 (cannabinoid receptor 1), which belongs to the guanine-nucleotide-binding protein (G-protein) coupled receptor family. In CB1 transfected HEK293 cells, the IC50 concentration of rimonabant was 13.6 nM and the EC50 concentration was 17.3 nM. Rimonabant was famous for its potent anorectic anti-obesity ability for decades and has been demonstrated to effectively reduce body weight by inducing a reduction in appetite. It also benefits for lowing cardiovascular metabolic risk events. However, it was withdrawn because of the severe byproduct in 2009, especially depression and anxiety. Mechanically, rimonabant promotes adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner by directly targeting to CB1. In vitro, rimonabant dose-dependently reduced ACAT activity in Raw264.7 macrophages and isolated peritoneal macrophages with an IC50 of 2.9 μM. Rimonabant also inhibited ACAT activity in CHO-ACAT1 and CHO-ACAT2 cells with an IC50 of 1.5 μM and 2.2 μM respectively. Rimonabant treatment blocks ACAT-related processes in macrophages, including oxysterol-induced apoptosis, and acetylated LDL-induced foam cell formation. Rimonabant was able to alter the cell cycle distribution in almost all type of cell lines and then significantly reduces cell growth and induces death in human colorectal cancer cells (DLD-1, CaCo-2 and SW620). However, rimonabant causes cell cycle arrest in DLD-1 cells without inducing apoptosis or necrosis. In vivo, Rimonabant significantly reduced the formation of abnormal crypt foci (ACF) before colorectal cancer formation in the oxidative azomethane-induced colon cancer model. In the experiment of long-term rimonabant treated obese Zucker rats, platelet-bound fibrinogen, serum levels of RANTES (normal T cell expression and secretion of regulatory proteins) and MCP-1 (monocyte chemoattractant protein-1) were decreased to the levels observed in lean Zucker rats.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  CHO cells	-	Function assay	-	Ability to displace [3H]-SR- 141716A binding to human CB1 receptor expressed in CHO cell membranes, Ki=8.9 nM	10465552
  CHO cells	-	Function assay	-	Antagonistic activity towards cannabinoid receptor 1 expressed as [3H]Arachidonic acid release in CHO cells, Kd=2.51 nM	14736243
  CHOK1 cells	-	Function assay	-	Antagonist activity at human CB1 receptor expressed in CHOK1 cells by luciferase assay, IC50=0.12 μM	18243711

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• 动物研究
  剂量	Mice: 0.3 mg/kg - 10 mg/kg[3] (p.o.), 10 mg/kg - 50 mg/kg[4] (p.o.)
  给药途径	p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT03204305	Cannabis Use Disorder ... more >> Cannabis Dependence, Continuous Collapse <<	Early Phase 1	Recruiting	May 31, 2020	United States, Maryland ... more >> Johns Hopkins Bayview Medical Center Recruiting Baltimore, Maryland, United States, 21224 Contact: Alisha Eversole    410-550-5254    aeverso1@jhmi.edu    Contact: Elise Weerts, Ph.D.    410-550-2781    eweerts@jhmi.edu Collapse <<
  NCT00628290	Schizophrenia	Phase 2	Completed	-	Germany ... more >> University of Cologne, Dept. of Psychiatry and Psychotherapy Cologne, NRW, Germany, 50924 Collapse <<
  NCT00636766	Carotid Atherosclerosis ... more >> Stroke Type 2 Diabetes Metabolic Syndrome Collapse <<	Not Applicable	Completed	-	Greece ... more >> General Hospital of Thessaloniki "Hippokratio" Thessaloniki, Greece Collapse <<

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