MCT Inhibitors

Research into a family of transporter proteins drives industry investment in cancer therapies

Most living cells acquire energy by breaking down glucose through a metabolic pathway known as glycolysis. Most cancer cells have a high rate of glycolysis resulting in the production of lactic acid, which the cancer cells need to get rid of to survive. Proteins found within the cell’s plasma membrane, known as moncarboxylate transporters (MCTs), help molecules to move across the membrane, including lactic acid. Inhibiting these proteins can cause a build-up of lactic acid in the cancer cells, eventually killing them.

Professor Andrew Halestrap and colleagues in the School of Biochemistry have pioneered research into MCTs and have identified and characterised four proteins within this family of transporter proteins. AstraZeneca discovered that some agents they were developing for immunosuppressive therapies were acting as MCT inhibitors.

The Bristol-based research was instrumental in increasing AstraZeneca’s understanding of the pharmacology of these agents. The mode of action of one of these potent inhibitors was characterised through a PhD Studentship funded by Astra Zeneca and a research collaboration, both at Bristol. As a result, Astra Zeneca initiated a new drug discovery programme directed towards identifying MCT4 specific inhibitors. Astra Zeneca subsequently gained support from Cancer Research UK to initiate clinical trials of a drug called AZD3965, which targets MCT1.

“[Halestrap’s research] over the last 20 years has had a major impact on our drug development programme focussed on potent and novel MCT1 inhibitors,” said Jeanette Wood, Vice President, Head of iScience at AstraZeneca.

“This work and other internal and external studies led us to initiate a new drug discovery programme directed towards identifying MCT4 specific inhibitors and to extend our collaboration with [the University of Bristol] to understand this anticancer treatment paradigm.”

Read the MCT inhibitors case study.

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