Elagolix

"目录号: HY-14791A

GPCR/G Protein-

(±)-SLV319是SLV319的消旋体。SLV319是有效选择性的大麻素-1 (CB-1) 受体拮抗剂，IC50值为22 nM。

Cannabinoid Receptor

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生物活性

Description

(±)-SLV319 is the racemate of SLV319. SLV319 is a potent and selective cannabinoid-1 (CB-1) receptor antagonist with anIC50of 22 nM.

IC50& Target

IC50: 22 nM (CB-1)[1]; Ki: 7.8 nM (CB-1)[2]

In Vitro

Cannabinoid receptor 1 (CB1R) antagonists appear to be promising drugs for the treatment of obesity, however, serious side effects have hampered their clinical application. Ibipinabant is a new, potent [Ki(CB1)=7.8 nM] and selective [Ki(CB2)=7.943 nM] CB1 antagonist [pA2 for arachidonic acid release in CHO cells=9.9] within vitropharmacological characteristics similar to rimonabant including inverse agonism and brain penetrance[3].

In Vivo

Ibipinabant (3 mg/kg) reduces unfasted glucose to a significantly greater degree than rimonabant at the same dose on days 17, 28 and 38. Chronic treatment with ibipinabant significantly attenuates the progression of diabetes in ZDF rats, blunting the increase in blood glucose and HbA1c over time. Ibipinabant also reduces the hyperinsulinemia apparent at 6-8 weeks of age and attenuates the dramatic reduction in insulin levels observed 1-2 weeks later[3].

References

[1].Chorvat RJ, et al. JD-5006 and JD-5037: peripherally restricted (PR) cannabinoid-1 receptor blockers related to SLV-319 (Ibipinabant) as metabolic disorder therapeutics devoid of CNS liabilities. Bioorg Med Chem Lett. 2012 Oct 1;22(19):6173-80.

[2].Lange JH, et al. Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB(1) cannabinoid receptor antagonists. J Med Chem. 2004 Jan 29;47(3):627-43.

[3].Rohrbach K, et al. Ibipinabant attenuates β-cell loss in male Zucker diabetic fatty rats independently of its effects on body weight. Diabetes Obes Metab. 2012 Jun;14(6):555-64.