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Substrate selective LTA4H LTB4 inhibition for inflammatory disorders
By Richard Butt
a collaboration with Dr Robert Snelgrove, Imperial College of Science, Technology & Medicine
Dr Robert Snelgrove is a Wellcome Trust Career Development Fellow at the National Heart and Lung Institute based at Imperial College. Dr Snelgrove has shown that the dual function of LTA4H to catalyse the formation of the pro-inflammatory lipid mediator LTB4 as well as the breakdown of PGP can be targeted individually by small molecule inhibitors. By inhibiting only the function of LTA4H to generate LTB4, it is possible to reduce the pro-inflammatory LTB4-driven response observed in a range of inflammatory diseases, whilst allowing the potent chemoattractant PGP to be degraded. This approach differentiates significantly from previous non substrate-selective agents tested clinically in inflammatory disease. Apollo and Dr Snelgrove will collaborate to run a discovery program to translate early hit substrate-selective LTA4H inhibitors into potential drug candidates.
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