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Research finds chemical compounds pointing to new therapeutic avenues for an aggressive blood cancer

The research was featured on the front cover of the journal Oncotarget

Scientists at the University of Sussex have identified a small chemical compound that is able to interfere with a protein-protein interaction that is critically important for the onset of an aggressive type of blood cancer; T-cell Acute Lymphoblastic Leukaemia (T-ALL).

The researchers, including Dr Erika Mancini and Dr Leanne Harris of the School of Life Sciences, argue that their findings have the potential to provide an alternative approach to developing novel drugs for the disease.

In their paper, published in Oncotarget and featured on the cover of the issue, the researchers demonstrated that the inhibitive action of this small chemical compound comes from its ability to bind to the protein LMO2, which is normally involved in the production of red blood cells.

They demonstrated that when the compound binds to LMO2, it causes a change in the shape of the molecule, which then renders it incapable of engaging in the cancerogenic protein-protein interaction that cause the onset of this type of Leukaemia.

Dr Mancini said: “T-cell Acute Lymphoblastic Leukaemia (T-ALL) is an aggressive blood cancer with current therapies limited to prolonged and gruelling cycles of chemotherapy and radiotherapy. While effective, these treatments are associated with significant, long-term adverse effects, particularly in young children. Additionally, patients presenting with relapsed T-ALL have a poor prognosis with current treatments.

“Targeting this critical protein-protein interaction (PPI) will provide us with an alternative approach to developing novel drugs for T-ALL. We plan to exploit the ability of small molecules to interfere with the shape of LMO2 to engineer specific therapeutics that can improve the treatment and prognosis for T-ALL patients.”

The research also provides evidence that using small molecules to modulate protein conformations, when these are key to mediating oncogenic interactions, can be used more widely as an approach to drug discovery.

Small molecule inhibits T-cell acute lymphoblastic leukaemia oncogenic interaction through conformational modulation of LMO2 is published in Oncotarget.


By: Jessica Gowers
Last updated: Tuesday, 23 June 2020

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