QUANTIFICATION OF SUBSTRATE AND INHIBITOR BINDING TO WILD TYPE AND MUTANT ISOCITRATE DEHYDROGENASE (IDH1) BY NON-DENATURING MASS SPECTROMETRY

摘要

A single point R132H mutation of human isocitrate dehydrogenase 1 (IDH1) is responsible for inhibition of epigenetic regulators and is associated with a variety of cancers including over 70% of gliomas and 30% of myeloid leukemias. Inhibitors of the R132H IDH1 isoform are currently in preclinical and clinical trials. We present 'native' (non-denaturing) MS data on the binding of several of these inhibitors to IDH1 and we compare the results with data from other methods.