Nathaniel Gray, PhD, Professor of Chemical and Systems Biology, School of Medicine; Associate Director, Therapeutics Discovery, Stanford Cancer Institute; Institute Scholar, ChEM-H Institute, Stanford University School of Medicine, Palo Alto, CA

Research Description: Dr. Gray’s work combines the disciplines of combinatorial, medicinal chemistry, and small molecule mechanism of action studies and brings this expertise to this Program. They contributed to the development of an approved drug for the treatment of non-small cell lung cancer, Ceritinib, an inhibitor of the EML4-ALK oncoprotein, and several kinase inhibitors currently undergoing clinical evaluation. His team and he were also responsible for developing siponimod, an agonist of the sphingosine-1-phosphate receptors which is used for the treatment of multiple sclerosis (MS). They have further contributed to the basic elucidation of new kinase inhibitory mechanisms such as the discovery of the first allosteric inhibitors of Bcr-Abl (GNF-2/5), the discovery of the first potent inhibitors of EML4-ALK kinase (TAE684), the development of the first mutant specific inhibitors of T790M EGFR (WZ4002), the first covalent inhibitors of JNK (JNK-IN-8), the first selective and brain penetrant inhibitors of LRRK2, and the first covalent inhibitors of CDK7 (THZ1) and CDK12/13 (THZ531). More recently, they have been contributing to the advancement of ‘proximity-based’ therapeutics such as ligase-recruiting degraders and transcription factor dimerizing compounds (TCIPSs). In addition to his lab’s work in cancer, they have a substantial program in metabolism, obesity, and feeding control. Dr. Gray collaborates extensively with members of the NORC. Very recent work from Jon Long has identified the PTER as the N-acetyl taurine hydrolase that regulates feeding and obesity. They have developed a new inhibitor of PTER that may serve as a new obesity therapeutic. Moreover, they are working to provide libraries of kinase inhibitors to multiple labs to find new regulatory kinase regulatory pathways. They have worked with Peter Jackson’s lab to define kinases regulating lipotoxicity and control of ciliation and obesity signaling.