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Kinase Inhibitors as drug targets are currently at the peak of research and development. New screening platforms and libraries are available - but new challenges for the industry have evolved.
What is it that the kinase community is currently struggling with? What are the top challenges that need to be addressed in a focused assembly of knowledgeable leaders in the field? Answers to these and many other questions will be covered in this conference.
12:30 - 1:30 pm Conference Registration
1:30 Chairperson’s Remarks
1:40 Scaffold-Based Inhibitor Design Strategies Targeting Type II and Allosteric Sites: Future Beyond the Kinase Domain
Hariprasad, Vakayalapati, M. Pharm., Ph.D., Chief Scientist, Medicinal Chemistry, Center for Investigational Therapeutics, Huntsman Cancer Institute
Finding selective protein kinase inhibitors by targeting ATP binding site is one of the major difficulties due to the significant homology
exist within the substrate binding site.The recently published crystal structure complexes revealed that the binding sites beyond the ATPbinding site termed as Type II hydrophobic site. Whereas the inactive conformation of DFG motif of Type II site extends out further creating additional hydrophobic site referred as allosteric site. Targeting Type II and allosteric sites could possibly achieve greater selectivity due to the non-conserved amino acid residue pocket representing these two sites. Scaffold-Based design approaches together with virtual ligand screening methods will be presented with our success in finding conformational specific small-molecule kinase inhibitors.
2:10 Fragments and Drug Discovery for Kinase Targets
Roderick E. Hubbard, Ph.D., Senior Fellow, Research, Vernalis, Ltd.
Over the past six years, we have used fragment and structure-based methods to discover and optimise hit and lead series against a number of kinase targets. I will review some of the lessons learnt in projects that have resulted in clinical candidates (chk1), tools to probe the biology of the target (PDPK1), or interesting phenomena in ligand binding (chk1 and cdk2). In addition, I will review issues of selectivity, binding affinity of fragments, non-ATP site binding and observations on attempting to triage the very high hit rates observed (more than 100 hits).
2:40 Discovery of Kinase Inhibitors Using Structure-Based Design
3:10 Networking Refreshment Break in the Exhibit Hall
3:45 Computational Prediction of Kinase Inhibitor Selectivity for On and Off Targets
Roger S. Armen, Ph.D., Assistant Professor, Department of Pharmaceutical Sciences, Thomas Jefferson University
Computational profiling to predict kinase inhibitor selectivity can be used to incorporate the requirements of selectivity as a first initial step of the inhibitor design process. Our approach to this problem is a combination of homology modeling, CHARMM-based molecular docking and free energy calculations. Preliminary results for predicting the selectivity of 9 diverse kinase inhibitors against a panel of 105 human kinases demonstrate a reasonable predictive power for the identification of on and off targets.
4:15 Sponsored Presentation (Opportunity Available)
4:45 Talk Title to be Announced
Li Yan, M.D., Ph.D., Associate Director Clinical Oncology, Merck
5:15 Expert Panel Discussion: How much of a Challenge is the Selectivity of Kinase Inhibitors?
5:45 End of Day