The anti-cancer efficacy of a novel phenothiazine derivative is independent of dopamine and serotonin receptor inhibition.

ABSTRACT:

Introduction

An attractive, yet unrealized, goal in cancer therapy is repurposing psychiatric drugs that can readily penetrate the blood-brain barrier for the treatment of primary brain tumors and brain metastases. Phenothiazines (PTZs) have demonstrated anti-cancer properties through a variety of mechanisms. However, it remains unclear whether these effects are entirely separate from their activity as dopamine and serotonin receptor (DR/5-HTR) antagonists.

Methods

In this study, we evaluated the anti-cancer efficacy of a novel PTZ analog, CWHM-974, that was shown to be 100-1000-fold less potent against DR/5-HTR than its analog fluphenazine (FLU).

Results

CWHM-974 was more potent than FLU against a panel of cancer cell lines, thus clearly demonstrating that its anti-c

SUBMITTER: Vanneste M 

PROVIDER: S-EPMC10613967 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature