The results of a productive collaboration between Domainex and Oxford University have been published in a recent Nature Communications paper titled "Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment".
Domainex scientists, including Dr Philip Fallon and Dr Lydia Lee, designed and synthesised a new class of drug-like inhibitors of the RAS-effector interaction, working in close collaboration with a team led by Professor Rabbitts at Oxford University.
These compounds were also profiled by the Oxford team in BRET-based RAS cellular biosensor assays.
The RAS family of proteins represent a well-known cancer target that is notoriously difficult to inhibit with small-molecules. Fragment-based drug design, guided by X-ray crystallography, was used by our team to invent a novel series of inhibitors with good cellular efficacy, and pharmacokinetic properties suitable for in vivo studies. This is the first published study of structure-based design of direct RAS-effector inhibitors in this region of the crystal structure.
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Dr Tom Mander
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