Description:

Title: "From concept to clinic: a platform for discovery of highly selective, small molecule therapeutic candidates and in vivo molecular probes for protein kinase targets".

Abstract: The first approved protein kinase inhibitor drug in 2001 was followed by a rapid expansion of approved tyrosine kinase inhibitor drugs and more recently serine/threonine (S/T) kinase inhibitors. The findings that many kinase inhibitors bind to multiple targets, including other kinase targets, led to the postulation that selective targeting of a kinase active site would be essentially impossible due to the conservation of catalytic domains across the kinome and the high levels of ATP in eukaryotic cells. Further, the added barrier of only ~2% of small molecule drugs having adequate blood brain barrier distribution resulted in neglect of CNS protein kinases as potential therapeutic targets. To date, there are only two protein kinase inhibitors approved for CNS use. A team of highly talented Northwestern University students and postdoctoral fellows filled the approach gap by developing a platform for design, discovery and development of novel S/T protein kinase inhibitors with high target selectivity and in vivo utility for CNS disorders. Continued development by our lab and collaborators is delivering novel small in vivo molecular probes for deconvoluting kinase mediated pathophysiology pathways and therapeutic candidates.

Speaker: Daniel Martin Watterson, BS, PhD, NAI; John G. Searle Professor of Biochemistry & Molecular Biology, Northwestern University, Professor of Pharmacology, Feinberg School of Medicine