Mechanism of a New Class of Highly Specific Src Inhibitors
Our group wants to understand the molecular mechanism of signaling proteins and how small molecule ligands and drugs can modulate their activity. We are focusing on two projects: (1) Solution dynamics of protein tyrosine kinases involved in cancer and (2) Substrate spectrum of ubiquitin ligases and conjugating enzymes in aging.
In collaboration with David Liu (HHMI/Harvard) we developed and characterized in molecular detail potent macrocyclic inhibitors of Src kinase and its cancer-associated gatekeeper mutant. Our work establishes that macrocycles can inhibit protein kinases through a bi-substrate competitive mechanism with high potency and exceptional specificity, reveals the precise molecular basis for their desirable properties, and provides new insights into the development of Src-specific inhibitors with potential therapeutic relevance.
Markus Seeliger is Assistant Professor in the Department of Pharmacological Sciences at Stony Brook University Medical School. For more information please visit: http://www.pharm.stonybrook.edu/seeliger