Characterizing Type III Kinase Inhibitor Using Laser-Free Flash Oxidation (Fox™) Hydroxyl Radical Protein Footprinting

GenNext Technologies

ABL1 is a protooncogene that encodes Abl tyrosine kinase and with ATP it is involved in cell division, adhesion, differentiation, and response to stress. The SH3 domain that negatively regulates Abl Kinase can be deleted resulting in an oncogene. ABL1 gene has also been found fused to translocation partner genes and is associated with gastrointestinal system cancer, colorectal and stomach cancer, and leukemia. Non-allosteric Abl kinase inhibitors have shown high levels of secondary resistance and severe off-target drug effects resulting in the need for allosteric inhibitors with high specificity for Abl kinase including, GNF-5. The allosteric inhibitor, GNF-5, binds specifically to Abl’s myristate binding pocket inducing the active/open conformation of Abl to the inactive/closed conformation. Learn how the Fox™ System identified both binding site and allosteric changes from binding for both a native ligand and an allosteric inhibitor for Abl Kinase.