Ki: 8.5 nM
4-Quinolone-3-Carboxamide Furan CB2 Agonist is a high-affinity ligand of CB2.
The endocannabinoid system consists of endogenous cannabinoids (endocannabinoids), cannabinoid receptors (primarily CB1 and CB2), and the enzymes that synthesize and degrade endocannabinoids.
In vitro: Previous study found that 4-Quinolone-3-Carboxamide Furan CB2 Agonist (4g) was devoid of any potential “indirect” agonist activity at cannabinoid receptors, exerted by prolonging the lifespan of endocannabinoids because 4g at up to a 10 μM concentration did not inhibit anandamide or 2-AG degradation by FAAH or MAGL, respectively. In cytotosicity study, 4g was tested at 1 μM and the results showed that it exhibited very low or no cytotoxicity, the cell viability being above 95% after a 72 h treatment [1].
In vivo: In animal study, 4g was found to have antinociceptive activity in the formalin test in mice. Moreover, 4g was very potent with maximal effect being reached at the 1 mg/kg dose and efficacious also on the first phase of the nocifensive response. The effect of 4g could be strongly reduced by the addition of AM630, a CB2-selective antagonist/inverse agonist, therefore demonstrating that 4g might act as a potent and selective CB2 agonist [1].
Clinical trial: Up to now, 4-Quinolone-3-Carboxamide Furan CB2 Agonist is still in the preclinical development stage.
Reference:
[1] S. Pasquini, M. De Rosa, V. Pedani, et al. Investigations on the 4-quinolone-3-carboxylic acid motif. 4. Identification of new potent and selective ligands for the cannabinoid type 2 receptor with diverse substitution patterns and antihyperalgesic effects in mice. Journal of Medicinal Chemistry 54, 5444-5453 (2011).