NV-5138 hydrochloride is a leucine analog and is the first selective and orally active brain mTORC1 activator, binding to Sestrin2. NV-5138 hydrochloride can be used in the research of antidepressants [1] [2].

NV-5138 demonstrates nearly complete (100%) oral bioavailability and an elimination half-life of approximately 3 hours in plasma, observed after both intravenous and oral administration in male Sprague-Dawley rats weighing 250-400 g. At a dosage of 160 mg/kg, administered orally in a single dose, it significantly enhances the levels of phospho-mTOR and its downstream targets, phospho-p70S6K1 and phospho-4EB-P1, in synaptosomal preparations of the prefrontal cortex (PFC), indicating rapid biological activity [1][2]. Furthermore, chronic administration of NV-5138 (80 mg/kg, orally, daily for 7 days) has been found to exert antidepressant effects. Experimental dosages ranged from 40 to 160 mg/kg, with modes of administration including both single and daily doses for a period up to 7 days, underscoring its therapeutic potential [2]. Pharmacokinetic assessments were conducted at 1 mg/kg for intravenous and 5 mg/kg for oral dosages, establishing its pharmacokinetic profile [1].