Synergistic Effects of Tranylcypromine and NRF2 Inhibitor: A Repurposing Strategy for Effective Cancer Therapy

ChemMedChem. 2023 Dec 14;18(24):e202300282. doi: 10.1002/cmdc.202300282. Epub 2023 Nov 30.

Abstract

Drug repurposing has emerged as an attractive strategy for accelerating drug discovery for cancer treatment. In this study, we investigated combining Tranylcypromine (TCP) with a number of well-characterized drugs. Among these combinations, NRF2 inhibitor (ML385) exhibited synergistic effects in combination with TCP. Specifically, our results showed that the combination of TCP and ML385 resulted in a significant reduction in tumor proliferation while neither drug affected cancer cell growth meaningfully on its own. While further studies are needed to understand fully the extent of the synergistic efficacy, the underlying respective mechanisms and the potential side effects of this approach, our study has yielded a promising start for the development of an effective combination cancer therapy.

Keywords: Nrf2; combination cancer therapy; drug repurposing; gene knockout; synergistic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Repositioning / methods
  • Humans
  • NF-E2-Related Factor 2 / antagonists & inhibitors
  • Neoplasms* / drug therapy
  • Tranylcypromine* / pharmacology
  • Tranylcypromine* / therapeutic use

Substances

  • NF-E2-Related Factor 2
  • Tranylcypromine

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