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LY3027788 hydrochloride

Catalog No. T38790 CAS 1377615-55-8

LY3027788 hydrochloride is a diester analog of LY3020371, a selective antagonist of the metabotropic glutamate 2 and 3 receptors (mGlu2/3). It serves as a highly potent and orally bioavailable prodrug of LY3020371. Notably, LY3027788 hydrochloride exhibits antidepressant efficacy.

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LY3027788 hydrochloride Chemical Structure

LY3027788 hydrochloride, CAS 1377615-55-8

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Description	LY3027788 hydrochloride is a diester analog of LY3020371, a selective antagonist of the metabotropic glutamate 2 and 3 receptors (mGlu2/3). It serves as a highly potent and orally bioavailable prodrug of LY3020371. Notably, LY3027788 hydrochloride exhibits antidepressant efficacy.
In vitro	LY3027788 administered orally at single doses ranging from 4.8 to 27 mg/kg demonstrably induces antidepressant-like effects by reducing immobility times in the forced-swim test in mice, and at doses between 4.8 and 16 mg/kg, it amplifies the locomotor stimulant effects of quinpirole (16 mg/kg) in a locomotor activity assay in mice. Additionally, at doses from 10 to 30 mg/kg, LY3027788 dose-dependently prolongs wakefulness in rats without causing subsequent excessive sleepiness. Furthermore, a single oral dose of LY3027788 ensures the rapid and dose-proportional presence of the active metabolite LY3020371 in the plasma of both mice (4.8-27 mg/kg) and rats (3-30 mg/kg).
In vivo	LY3027788, when administered orally at doses ranging from 4.8 to 27 mg/kg, significantly reduces immobility times in mice during the forced-swim test, indicating antidepressant-like effects. At doses between 4.8 and 16 mg/kg, it also amplifies the locomotor stimulant effects of quinpirole in mice, particularly noticeable at a quinpirole dose of 16 mg/kg. Furthermore, administering LY3027788 in doses from 10 to 30 mg/kg increases wakefulness in rats, without causing subsequent hypersomnolence. Additionally, a single oral dose leads to a rapid and dose-dependent increase in the concentration of LY3020371, its active metabolite, in the plasma of both mice (4.8-27 mg/kg) and rats (3-30 mg/kg). In SPN Model using male Sprague-Dawley mice weighing 20-25 g, a single oral dose 60 minutes before testing revealed LY3027788 to be potent and efficacious, with a minimal effective dose of 16 mg/kg in the forced-swim assay and an ED_60 of 8.2 mg/kg.

Molecular Weight	628.03
Formula	C25H32ClF2NO11S
CAS No.	1377615-55-8

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

References and Literature

1. Witkin JM, et, al. Comparative Effects of LY3020371, a Potent and Selective Metabotropic Glutamate (mGlu) 2/3 Receptor Antagonist, and Ketamine, a Noncompetitive N-Methyl-d-Aspartate Receptor Antagonist in Rodents: Evidence Supporting the Use of mGlu2/3 Antagonists, for the Treatment of Depression. J Pharmacol Exp Ther. 2017 Apr;361(1):68-86. 2. Witkin JM, et, al. mGlu2/3 receptor antagonism: A mechanism to induce rapid antidepressant effects without ketamine-associated side-effects. Pharmacol Biochem Behav. 2020 Mar;190:172854.

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Keywords

LY3027788 hydrochloride 1377615-55-8 LY-3027788 hydrochloride LY3027788 Hydrochloride LY 3027788 Hydrochloride LY-3027788 Hydrochloride inhibitor inhibit

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