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NV-5138

  Cat. No.:  DC60095   Featured
Chemical Structure
2095886-80-7
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More than 5000 active chemicals with high quality for research!
Field of application
NV-5138 is an orally and centrally active small-molecule drug for the treatment of major depressive disorder (MDD). It directly and selectively activates the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway by binding to and modulating sestrin2, a leucine amino acid sensor and upstream regulatory pathway. The mTORC1 pathway is the same signaling pathway that the NMDA receptor antagonist ketamine activates in the medial prefrontal cortex (mPFC) to mediate its rapid-acting antidepressant effects. A single oral dose of NV-5138 has been found to increase mTORC1 signaling and produce synaptogenesis in the mPFC and to induce rapid antidepressant effects in multiple animal models of depression.
Chemicals PropertiesBiological activity COA & MSDSRelated productsDatasheet
Cas No.: 2095886-80-7
Chemical Name: 4-(Difluoromethyl)-L-leucine
Synonyms: 06CA9QMG6Z;4-(difluoromethyl)-L-leucine;N[C@H](C(=O)O)CC(C(F)F)(C)C;((S)-2-Amino-5,5-difluoro-4,4-dimethylpentanoic acid;Pentanoic acid, 2-amino-5,5-difluoro-4,4-dimethyl-, (2S)-;K94
SMILES: FC([H])(C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[C@@]([H])(C(=O)O[H])N([H])[H])F
Formula: C7H13F2NO2
M.Wt: 181.1804
Purity: >98%
Sotrage: 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO
Description: NV-5138, a leucine analog, is the first selective and orally active brain mTORC1 activator, binding to Sestrin2. NV-5138 possesses rapid antidepressant effects[1][2].
Target: mTORC1[1].
In Vivo: NV-5138 is found to be essentially 100% orally bioavailable with an elimination half-life in plasma of ~ 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: Produces 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.
References: [1]. Sengupta S, et al. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. [2]. Kato T, et al. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. J Clin Invest. 2019 Apr 16;129(6):2542-2554.
MSDS
COA
LOT NO. DOWNLOAD
2018-0101
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