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Hunting for hits for E3 ligases


E3 ligases are interesting drug targets for a number of different disease indications, however there are a number of challenges in working with these targets. IDOL (inducible degrader of the LDL receptor (LDLr)) is a cytosolic E3 ligase which catalyses the ubiquitination of LDLr and targets the receptor for degradation in the cell. Based on internal knock out mouse data an inhibitor of IDOL will increase LDLr levels and subsequently decrease circulating LDL-cholesterol .

Within discovery sciences we design screening strategies and cascades specific for each target and to complement this we have established a number of hit identification approaches. In the case of IDOL multiple hit finding approaches have been executed using both cell based and binding assays. In addition secondary in vitro assays have enabled hit evaluation and characterization in order to understand interaction with the target and biological effects.
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