The human protein kinase superfamily comprises over 500 members that operate in nearly
every signal transduction pathway and regulate essential cellular processes. Deciphering
the functional roles of protein kinases with small-molecule inhibitors is essential to enhance
our understanding of cell signaling and to facilitate the development of new therapies.
However, it is rather challenging to identify selective kinase inhibitors because of the
conserved nature of the ATP binding site. A number of chemical-genetic approaches have …

In the first part of my thesis, I describe erythropoietin-producing human hepatocellular
carcinoma (Eph) receptor tyrosine kinases (RTKs) regulating a variety of dynamic cellular
events, including cell protrusion, migration, proliferation, and cell fate determination. The
usage of small-molecule inhibitors of Eph kinases are valuable tools for dissecting the
physiological and pathological roles of Eph. Unfortunately, there is a lack of small-molecule
inhibitors that are available to be selective for individual Eph isoforms due to the high …