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NSI-189 structure.svg
Clinical data
  • US: N (Not classified yet)
Routes of
Legal status
Legal status
Pharmacokinetic data
Biological half-life 17.4–20.5 hours[1]
CAS Number
PubChem CID
Chemical and physical data
Formula C22H30N4O
Molar mass 366.4998 g/mol
3D model (JSmol)

NSI-189 is an experimental, potential antidepressant that is under investigation by Neuralstem, Inc. for the treatment for major depressive disorder (MDD), as well as for cognitive impairment and neurodegeneration.[2][1][3] Research into NSI-189 has been funded by the Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH).[4]

The compound's activity was discovered using phenotypic screening with a library of 10,269 compounds to identify compounds that promoted neurogenesis in vitro.[3] As of 2016 the target of the compound was unknown but it appeared to promote neurogenesis in rodents.[2][3]

NSI-189 completed a phase I clinical trial for MDD in 2011, where it was administered to 41 healthy volunteers.[5] A phase Ib clinical trial for treating MDD in 24 patients started in 2012 and completed in July 2014, with results published in December 2015.[1][6] In July 2017, it was announced that a phase II clinical trial with 220 patients failed to meet its primary effectiveness endpoint in MDD.[7] Upon the announcement, Neuralstem stock plummeted by 61%.[8]

In addition to MDD, Neuralstem has said that it intends to pursue clinical development of NSI-189 for a variety of other neurological conditions, including traumatic brain injury, Alzheimer's disease, post-traumatic stress disorder, stroke, and to prevent cognitive and memory decline in aging.[2][4]

See also[edit]


  1. ^ a b c d Fava, M; Johe, K; Ereshefsky, L; Gertsik, L G; English, B A; Bilello, J A; Thurmond, L M; Johnstone, J; Dickerson, B C; Makris, N; Hoeppner, B B; Flynn, M; Mischoulon, D; Kinrys, G; Freeman, M P (2015). "A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients". Molecular Psychiatry. ISSN 1359-4184. doi:10.1038/mp.2015.178. 
  2. ^ a b c Eric E. Bouhassira (15 June 2015). The SAGE Encyclopedia of Stem Cell Research. SAGE Publications. pp. 843–. ISBN 978-1-4833-4767-7. 
  3. ^ a b c Neuralstem (March 2016), Neuralstem Inc. March 2016 Corporate Presentation (PDF), archived from the original (PDF) on 31 January 2017, retrieved 25 March 2016 
  4. ^ a b FDA Approves Neuralstem To Treat Final Cohort In NSI-189 Phase Ib Trial In Major Depressive Disorder
  5. ^ Single-Dose Pharmacokinetics (PK) Study of Novel Neurogenic Compound NSI-189
  6. ^ Multiple-Dose Pharmacokinetics (PK), and Pharmacodynamic (PD) Effect of NSI-189 Phosphate in Depression Patient Subjects
  7. ^ https://globenewswire.com/news-release/2017/07/25/1057673/0/en/Neuralstem-Announces-Top-line-Phase-2-Data-of-NSI-189-for-Major-Depressive-Disorder.html
  8. ^ http://www.marketwatch.com/story/neuralstem-stock-halted-on-news-of-mid-stage-clinical-trial-miss-2017-07-25-8912741

External links[edit]

  • McIntyre RS, Johe K, Rong C, Lee Y (2017). "The Neurogenic Compound, NSI-189 Phosphate: a Novel Multi-Domain Treatment Capable of Pro-Cognitive and Antidepressant Effects". Expert Opin Investig Drugs. PMID 28460574. doi:10.1080/13543784.2017.1324847.