Lysine-targeting covalent inhibitors

The PhD student will modify high affinity reversible ligands of mutant EGFR and mutant B-Raf with lysine-targeting electrophiles using structure based rational design. The student would then characterise their inhibitors using biochemical methods to establish kinetic parameters and compare with the wild-type proteins. The inhibitors would then be applied to cancer cells to establish kinome selectivity, off-target reactivity and wild-type/mutant cell therapeutic index.