NSI-189

• CAT Number: I008377
• CAS Number: 1270138-40-3
• Molecular Formula: C22H30N4O
• Molecular Weight: 366.4998
• Purity: ≥95%
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• 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 (CAT:I008377) is a niacinamide piperazine derivative. It can stimulate the neurogenesis of human hippocampal neural stem cells, so it is promising for major depression, Alzheimer’s disease, center and other brain diseases. This product is used for organic synthesis, drug development, and other scientific research purposes.

Overview of Clinical Research

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

Reference

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.