NV-5138 is a sestrin modulator and mammalian target of rapamycin protein complex 1 (mTORC1) activator.1 It binds to sestrin 2 (Kd = 1.49 ?M) and induces dissociation of sestrin 2 from the multimeric mTORC1 inhibitory complex GATOR2 and mTORC1 activation when used at concentrations ranging from 30 to 100 ?M. NV-5138 (40, 80, or 160 mg/kg) reduces immobility time in the forced swim test and latency to feed in the novelty-suppressed feeding test, indicating antidepressant- and anxiolytic-like activity, respectively, in rats, effects that can be reversed by the mTORC1 inhibitor rapamycin .2 It also reverses behavioral and synaptic deficits in a rat model of chronic stress-induced depression.
1.Sengupta, S., Giaime, E., Narayan, S., et al.Discovery of NV-5138, the first selective Brain mTORC1 activatorSci. Rep.9(1)4107(2019) 2.Kato, T., Pothula, S., Liu, R.-J., et al.Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activationJ. Clin. Invest.129(6)2542-2554(2019)