NSI-189

Appearance:white to off-white solid powder
Purity: > 98%

Cat No:	I008377
Cas No:	1270138-40-3
Product-Name:	NSI-189
InChI:	InChI=1S/C22H30N4O/c1-18(2)10-12-24-21-20(9-6-11-23-21)22(27)26-15-13-25(14-16-26)17-19-7-4-3-5-8-19/h3-9,11,18H,10,12-17H2,1-2H3,(H,23,24)
InChIKey:	DYTOQURYRYYNOR-UHFFFAOYSA-N
SMILES:	O=C(N1CCN(CC2=CC=CC=C2)CC1)C3=CC=CN=C3NCCC(C)C

NSI-189 is a nootropic and neurogenic research chemical derived from nicotinamide and pyrazine created by Neuralstem, Inc. NSI-189 has been shown to stimulate neurogenesis of human hippocampus-derived neural stem cells in vitro and in vivo. NSI-189 has been shown to increase the hippocampal volume of healthy adult mice by 20%. NSI-189 successfully completed a phase 1 clinical trial in 2011 where it was administered to 41 healthy volunteers, with no adverse effects reported. A phase 1B clinical trial for treating major depressive disorder in 24 patients started in 2012, with study completion expected in January 2014. Assuming positive outcomes in the phase 1b clinical trial, Neuralstem intends to pursue further clinical trials for a variety of encephalopathic conditions including major depressive disorder, traumatic brain injury, Alzheimer/'s disease, post-traumatic stress disorder, troke and natural aging.

1. Expert Opin Investig Drugs. 2017 Jun;26(6):767-770. doi: 10.1080/13543784.2017.1324847. Epub 2017 May 8.
The neurogenic compound, NSI-189 phosphate: a novel multi-domain treatment capable of pro-cognitive and antidepressant effects.
McIntyre RS(1)(2)(3), Johe K(4), Rong C(2), Lee Y(2).

Author information:
(1)a Department of Psychiatry , University of Toronto , Toronto , Canada.
(2)b Mood Disorders Psychopharmacology Unit , University Health Network , Toronto , Canada.
(3)c Brain and Cognition Discovery Foundation , Toronto , Canada.
(4)d Neuralstem , 20271 Goldenrod Lane, Germantown , MD 20876 , USA.

INTRODUCTION: Alterations in neurogenic and neurotrophic processes as well as intracellular signalling cascades provides the basis for hypothesizing that neurogenic agents may be therapeutic across multiple RDoC-defined domains (e.g. positive valence systems, general cognitive processes). Moreover, using the DSM-5 taxonomy, neurogenic agents may mitigate symptoms in adults with depressive and bipolar disorders as well as individuals with cognitive disorders. Areas covered: NSI-189 is a benzylpiperizine-aminiopyridine, a novel chemical entity that stimulates neurogenesis of human hippocampus-derived neural stem cells in vitro and stimulates neurogenesis in murine hippocampus in vivo. Emerging evidence also indicates that NSI-189 phosphate has regionally specific effects insofar as neurogenesis is observed largely in the subventricular zone of the hippocampus. Results from a preliminary proof of concept study suggests that NSI-189 may be capable of mitigating depressive symptoms and improve cognitive function in adults with DSM-5-defined Major Depressive Disorder (MDD). Expert opinion: Preliminary proof-of-concept studies indicate both antidepressant and procognitive effects. Beneficial effects in cognitive-emotional processing as well as whether the procognitive effects are independent of antidepressant effects are vistas of future research. Taken together, NSI-189 is a multi-domain neurogenic compound with brain-therapeutic properties with potential therapeutic applications across disparate psychiatric disorders.