Citrate transporter inhibitors: possible new anticancer agents

Future Med Chem. 2022 May;14(9):665-679. doi: 10.4155/fmc-2021-0341. Epub 2022 Mar 31.

Abstract

The culmination of 80+ years of cancer research implicates the aberrant metabolism in tumor cells as a root cause of pathogenesis. Citrate is an essential molecule in intermediary metabolism, and its amplified availability to critical pathways in cancer cells via citrate transporters confers a high rate of cancer cell growth and proliferation. Inhibiting the plasma membrane and mitochondrial citrate transporters - whether individually, in combination, or partnered with complementary metabolic targets - in order to combat cancer may prove to be a consequential chemotherapeutic strategy. This review aims to summarize the use of different classes of citrate transporter inhibitors for anticancer activity, either individually or as part of a cocktail.

Keywords: anticancer; citrate; drug discovery; mitochondrial citrate transporter (CTP); plasma membrane citrate transporter (PMCT).

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carrier Proteins / metabolism
  • Carrier Proteins / therapeutic use
  • Citric Acid / metabolism
  • Citric Acid / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism

Substances

  • Antineoplastic Agents
  • Carrier Proteins
  • citrate-binding transport protein
  • Citric Acid