NSI-189 – (1270138-40-3)

ALTO-100, previously known as NSI-189, is a novel neurogenic compound under development for the treatment of major depressive disorder (MDD), bipolar depression, and post-traumatic stress disorder (PTSD). It is described as a hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator. ALTO-100’s exact mechanism of action is unknown, but it is thought to enhance BDNF signaling and increase neuroplasticity and neurogenesis in the hippocampus. The drug has been shown to increase hippocampal volume in rodents, although this effect was not significant in human clinical studies.

As of July 2024, ALTO-100 is in phase 2 clinical trials for MDD, bipolar depression, and PTSD, with a phase 3 trial for MDD being planned. Clinical trials have shown mixed results for the drug’s effectiveness in treating MDD, but significant cognitive and memory improvements have been observed. ALTO-100 is being developed by Alto Neuroscience, having been previously developed by Neuralstem, Inc.

The drug was identified through a neurogenesis functional screen and has been found to enhance hippocampal neuroplasticity and neurogenesis in multiple preclinical models. It does not interact with monoamine transporters, receptors, or amino acid targets, and is believed to work through indirect modulation of BDNF and its signaling. In a small phase 1 clinical study, ALTO-100 did not impact hippocampal or amygdalar volume in patients with MDD, but it did show cognitive and memory benefits in a phase 2 study.

ALTO-100’s development history includes phase 1 and phase 2 trials conducted by Neuralstem, with mixed results. The drug was acquired by Alto Neuroscience in 2021, which is now continuing its development. Other drugs under development by Alto Neuroscience include ALTO-203, ALTO-300, and ALTO-202, all targeting MDD.

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Sources:

https://en.wikipedia.org/wiki/NSI-189
https://www.medchemexpress.com/nsi-189.html
https://www.medkoo.com/products/6606
https://www.nature.com/articles/s41380-018-0334-8
https://pubmed.ncbi.nlm.nih.gov/32722729/
https://go.drugbank.com/drugs/DB16230