NV-5138

NV-5138
Clinical data
Routes of
administration		 By mouth[1]
Drug class Sestrin2 modulator; mTORC1 activator

NV-5138 is an orally and centrally active small-molecule drug which is under development by Navitor Pharmaceuticals for the treatment of major depressive disorder (MDD).[2][1][3] 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.[1][3][4] 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.[1][3] 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.[1][3] Like those of ketamine, these actions require the signaling of brain-derived neurotrophic factor (BDNF).[1] The antidepressant effects following a single dose of NV-5138 are long-lasting, with a duration of up to 7 days, and are similar to those of ketamine.[1][3] Based on these promising preclinical findings, efforts are underway to assess NV-5138 in clinical trials with human subjects.[1] As of July 2018, NV-5138 is in the preclinical phase of development for the treatment of MDD.[2]

See also

References

  1. 1 2 3 4 5 6 7 8 Duman RS (2018). "Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide". F1000Res. 7. doi:10.12688/f1000research.14344.1. PMC 5968361. PMID 29899972.
  2. 1 2 https://adisinsight.springer.com/drugs/800040858
  3. 1 2 3 4 5 Duman, R., Kato, T., Liu, R. J., Duman, C., Terwilliger, R., Vlasuk, G., ... & Sajah, E. (2017, November). Sestrin 2 Modulator NV-5138 Shows Ketamine-Like Rapid Antidepressant Effects via Direct Activation of mTORC1 Signaling. In Neuropsychopharmacology (Vol. 43, pp. S195-S195). Macmillan Building, 4 Crinan St, London N1 9Xw, England: Nature Publishing Group. https://www.nature.com/articles/npp2017264.pdf
  4. ↑ Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM (January 2016). "Sestrin2 is a leucine sensor for the mTORC1 pathway". Science. 351 (6268): 43–8. doi:10.1126/science.aab2674. PMC 4698017. PMID 26449471.


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