Effect of a Novel Antidepressant and Anticancer Nuc01 on Depression in Cancer Survivors

Area of Science:

• Pharmacology
• Oncology
• Neuroscience

Background:

• Depression in cancer survivors is often treated with serotonin and norepinephrine reuptake inhibitors (SNRIs).
• Lysine-specific demethylase 1 (LSD1) is a target for cancer therapy, as its inhibition suppresses cancer cell proliferation.
• Novel therapeutic strategies are needed to address both depression and cancer in survivors.

Purpose of the Study:

• To evaluate Nuc01, a novel trans-2-phenylcyclopropylamine (PCPA)-drug conjugate and prodrug of venlafaxine, for its potential dual therapeutic applications.
• To investigate Nuc01's efficacy as a triple reuptake inhibitor for depression.
• To assess Nuc01's potential as an LSD1 inhibitor with anticancer properties.

Main Methods:

• In vivo studies using the tail suspension test in mice to assess antidepressant potential.
• In vitro studies to determine Nuc01's binding affinity to LSD1 and its inhibitory concentration (IC50).
• Evaluation of Nuc01's effect on the proliferation of MDA-MB-231 cancer cells.

Main Results:

• Nuc01 dose-dependently reduced immobility time in mice, outperforming desmethylvenlafaxine, suggesting potent triple reuptake inhibition.
• Nuc01 effectively occupied the PCPA binding site within LSD1 with an IC50 of 530 nm.
• Nuc01 inhibited the proliferation of MDA-MB-231 cancer cells with an IC50 of 1130 nm.

Conclusions:

• Nuc01 exhibits dual functionality, acting as a potential triple reuptake inhibitor for depression treatment.
• Nuc01 demonstrates potential as an LSD1 inhibitor with anticancer properties.
• Nuc01 represents a promising novel therapeutic agent for addressing both depression and cancer.