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 is found to have essentially 100% orally bioavailable with an elimination half-life in plasma of approximately 3 h determined following intravenous and oral dosing in rats [1]. NV-5138 (160 mg/kg, po, single dose) rapidly increases levels of phospho-mTOR as well as the downstream targets, phospho-p70S6K1, and phosphor-4EB-P1, in synaptosomal preparations of PFC [2]. NV-5138 (80 mg/kg, po, daily for a total of 7 days) also produces antidepressant effects [2]. Animal Model: Male Sprague-Dawley rats weighing 250-260 g [2]. Dosage: 40, 80, 160 mg/kg. Administration: PO, single dose (160 mg/kg) or daily for a total of 7 days (40, 80 mg/kg). Result: Produced antidepressant effects. Animal Model: Male Sprague-Dawley (SD) rats weighed 250-400 g [1]. Dosage: 1 mg/kg, 5 mg/kg ( Pharmacokinetic Design ). Administration: I.V at 1 mg/kg and PO at 5 mg/kg. Result: Essentially 100% orally bioavailable with an elimination half-life in plasma of ~ 3 h.