MedKoo Cat#: 555979 | Name: NV-5138
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

NV-5138
NV-5138
CAS#2095886-80-7

Theoretical Analysis

MedKoo Cat#: 555979

Name: NV-5138

CAS#: 2095886-80-7

Chemical Formula: C7H13F2NO2

Exact Mass: 181.0914

Molecular Weight: 181.18

Elemental Analysis: C, 46.40; H, 7.23; F, 20.97; N, 7.73; O, 17.66

Price and Availability

Size Price Availability Quantity
10mg USD 550.00 2 Weeks
25mg USD 950.00 2 Weeks
50mg USD 1,650.00 2 Weeks
100mg USD 2,950.00 2 Weeks
1g USD 6,950.00 2 Weeks
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Related CAS #
No Data
Synonym
NV-5138; NV 5138; NV5138;
IUPAC/Chemical Name
Pentanoic acid, 2-amino-5,5-difluoro-4,4-dimethyl-, (2S)-
InChi Key
HRFIMCJTDKEPPV-BYPYZUCNSA-N
InChi Code
InChI=1S/C7H13F2NO2/c1-7(2,6(8)9)3-4(10)5(11)12/h4,6H,3,10H2,1-2H3,(H,11,12)/t4-/m0/s1
SMILES Code
O=C(O)[C@@H](N)CC(C)(C)C(F)F
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
To be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Biological target:
NV-5138, a leucine analog, is the first selective and orally active brain mTORC1 activator, binding to Sestrin2.
In vitro activity:
This study reports NV-5138, a novel orally bioavailable compound that binds to Sestrin2 and activates mTORC1 both in vitro and in vivo. Treatment with NV-5138 activates mTORC1 in leucine-starved unedited HEK-293T cells, but not in cells lacking all three Sestrins or the GATOR1 component Nprl3 indicating that compound activity requires an intact Sestrins/GATOR pathway (Fig. 2f,g). Reference: Sci Rep. 2019 Mar 11;9(1):4107. https://pubmed.ncbi.nlm.nih.gov/30858438/
In vivo activity:
The results demonstrate that a single dose of NV-5138 produced rapid and long-lasting antidepressant effects, and rapidly reversed anhedonia caused by chronic stress exposure. The antidepressant actions of NV-5138 required BDNF release as the behavioral responses are blocked by infusion of a BDNF neutralizing antibody into the medial prefrontal cortex (mPFC) or in mice with a knock-in of a BDNF polymorphism that blocks activity dependent BDNF release. NV-5138 administration also rapidly increased synapse number and function in the mPFC, and reversed the synaptic deficits caused by chronic stress. Reference: J Clin Invest. 2019 Apr 16;129(6):2542-2554. https://pubmed.ncbi.nlm.nih.gov/30990795/
Solvent mg/mL mM
Solubility
DMSO 25.0 137.98
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 181.18 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. J Clin Invest. 2019 Apr 16;129(6):2542-2554. doi: 10.1172/JCI126859. PMID: 30990795; PMCID: PMC6546461. 2. Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID: 30858438; PMCID: PMC6412019.
In vitro protocol:
1. Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID: 30858438; PMCID: PMC6412019.
In vivo protocol:
1. Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. J Clin Invest. 2019 Apr 16;129(6):2542-2554. doi: 10.1172/JCI126859. PMID: 30990795; PMCID: PMC6546461. 2. Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID: 30858438; PMCID: PMC6412019.
1: Hasegawa Y, Zhu X, Kamiya A. NV-5138 as a fast-acting antidepressant via direct activation of mTORC1 signaling. J Clin Invest. 2019 May 20;129(6):2207-2209. doi: 10.1172/JCI129702. PMID: 31107245; PMCID: PMC6546442. 2: Kato T, Pothula S, Liu RJ, Duman CH, Terwilliger R, Vlasuk GP, Saiah E, Hahm S, Duman RS. Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation. J Clin Invest. 2019 Apr 16;129(6):2542-2554. doi: 10.1172/JCI126859. PMID: 30990795; PMCID: PMC6546461. 3: Sengupta S, Giaime E, Narayan S, Hahm S, Howell J, O'Neill D, Vlasuk GP, Saiah E. Discovery of NV-5138, the first selective Brain mTORC1 activator. Sci Rep. 2019 Mar 11;9(1):4107. doi: 10.1038/s41598-019-40693-5. PMID: 30858438; PMCID: PMC6412019.