Protein Kinase Inhibitors in Research and Medicine

Professor Kevan is currently an Investigator of the Howard Hughes Medical Institute, Chair of the Department of Cellular and Molecular Pharmacology at UCSF and a Professor of Chemistry at UC Berkeley. He was inducted into the National Academy of Sciences (2010), the Institute of Medicine (2011), and the American Academy of Arts and Sciences (2011). His lab is most well-known for drugging the "undruggable" oncogene K-Ras (G12C) in 2013. In May of 2021 the drug sotorasib which binds to the same pocket on K-Ras (G12C) was approved for the treatment of lung cancer patients with this mutation. The field of K-Ras drug discovery is expanding quickly to hunt for drugs to target the other K-Ras mutants such as those which drive colon and pancreatic cancers which collectively represent almost 20% of all cancer patients world-wide. Kevan has been a co-founder of a number companies from their inception to public offering or acquisition and he is a co-founder of several currently private companies.

This new volume of Methods in Enzymology continues the legacy of this premier serial with quality chapters authored by leaders in the field. This is the first of two volumes covering protein kinase inhibitors in research and medicine, and includes chapters on such topics as fragment based screening, broad kinome profiling of kinase inhibitors, and designing drug resistant kinase alleles.

• 1. Catalytic Mechanisms and Regulation of Protein KinasesZhihong Wang and Philip A. Cole.2. A Structural Atlas of Kinases Inhibited by Clinically Approved DrugsQi Wang, Julie A. Zorn and John Kuriyan.3. Fragment-Based Approaches to the Discovery of Kinase InhibitorsPaul N. Mortenson, Valerio Berdini and Marc O’Reilly.4. Targeting Protein Kinases with Selective and Semi-Promiscuous Covalent InhibitorsRand M. Miller and Jack Taunton.5. The Resistance Tetrad: Amino Acid Hotspots for Kinome-Wide Exploitation of Drug-resistant Protein Kinase AllelesVeselin I Andreev and Patrick A Eyers6. FLiK: A Direct Binding Assay for the Identification and Kinetic Characterization of Stabilizers of Inactive Kinase Conformations Jeffrey R. Simar and Daniel Rauh7. Discovery of Allosteric Bcr-Abl inhibitors from Phenotypic Screen to Clinical CandidateNathanael S. Gray and Doriano Fabbro8. The Logic and Design of Analog-Sensitive (AS) Kinases and their Small Molecule InhibitorsMichael S. Lopez, Joseph Kliegman and Kevan M. Shokat