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Molecules Inhibit Cancer Metastasis and Multiple Sclerosis

An international team of scientists has identified potential inhibitors of cell membrane proteins involved in the spread of cancer to other parts of the body, and in the progression of autoimmune diseases such as multiple sclerosis.

The newly identified molecules strongly inhibit the action of the two chemokine receptors CXCR4 and ACKR3, which work together to regulate cell migration and are thus important in both cancer metastasis and autoimmune disease. The variant that bound most strongly to the CXCR4 receptor inhibited multiple sclerosis in a laboratory study.

“Scientists around the world are looking for ways of blocking the CXCR4 and ACKR3 receptors as a means of preventing or at least slowing down the cell migration that underlies the progression of these diseases,” says Prof Shaun McColl of the University of Adelaide. “We hope these new molecules will be the basis for the design of new drugs that will interfere with cancer metastasis and inhibit multiple sclerosis.”

The researchers identified twelve molecules of modified human protein that act against the receptors, four of them very strongly. They generated thousands of modified molecules of these natural human proteins and then screened them for their ability to bind to the target receptors. The method produced inhibitors specific to particular proteins.

“Cancer treatment is at the stage where the aim is to get more specific with treating different cancers so there are fewer side-effects of chemotherapy,” McColl said. “The next stage of this research will be to use molecular modelling to work out exactly where these molecules are binding to the receptors and how they are disrupting their function so they can be further modified for even greater specificity.”

The research has been published in the Journal of Biological Chemistry.