NSI-189

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

Cat No:	I008377
Cas No:	1270138-40-3
Product-Name:	NSI-189
IUPAC Name:	(4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino)pyridin-3-yl]methanone
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(cas 1270138-40-3) 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.

Originator Neuralstem
Developer Palisade Bio; University of California, San Diego
Class Antidepressants; Antihyperglycaemics; Neuroprotectants; Nootropics; Piperazines; Pyridines; Small molecules; Vascular disorder therapies
Mechanism of Action Neurogenesis stimulants
Orphan Drug StatusYes - Angelman syndrome
New Molecular Entity Yes
Available For Licensing Yes

1. Ann Clin Psychiatry. 2020 Aug;32(3):182-196.
NSI-189 phosphate, a novel neurogenic compound, selectively benefits moderately depressed patients: A post-hoc analysis of a phase 2 study of major depressive disorder.
Johe KK, Kay G, Kumar S, Burdick KE, McIntyre RS, Papakostas GI, Fava M.
BACKGROUND: NSI-189 phosphate (NSI-189) is a novel neurogenic molecule with pleiotropic properties, including antidepressant, procognitive, synaptoplastic, and neurotrophic activities demonstrated in preclinical studies. Its antidepressant activity is monoamine-independent. NSI-189 was previously tested in patients with recurrent major depressive disorder in an inpatient setting. METHODS: This study involved 220 patients randomized to an NSI-189 40-mg dose, NSI-189 80-mg dose, or placebo daily for 12 weeks. The study utilized the sequential parallel comparison design, in which the drug effect was tested in 2 separate stages of 6 weeks each. Herein, post-hoc analyses of the data are presented.
RESULTS: NSI-189's antidepressant effect increased when the participants' initial baseline depression severity was dichotomized along a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 30. The NSI-189 80-mg dose showed significant benefit over placebo when utilizing the MADRS-6 (P = .046) in the subgroup of patients who were moderately depressed (MADRS < 30) but was not significant in patients who were severely depressed (MADRS ≥30). More pronounced procognitive effects were also observed in the moderate subgroup relative to the severe subgroup or the whole study group, in which 11/36 (31%), 5/36 (14%), or 7/36 (19%) of CogScreen variables significantly improved, respectively. CONCLUSIONS: These results suggest that NSI-189 is effective as a safe adjunctive therapy, with most compelling antidepressant and procognitive benefits noted in patients with moderate depression.