Nathanael Gray is a Professor of Chemical and Systems Biology at Stanford University. His research utilizes tools of synthetic chemistry, protein biochemistry, and cancer biology to discover and validate new strategies for the inhibition of anticancer targets. Dr. Gray’s research has had a broad impact on the areas of kinase inhibitor design and in circumventing drug resistance. Some of the notable accomplishments of Dr. Gray’s team at Genomics Institute of the Novartis Research Foundation (GNF) in San Diego, California, include discovering the first allosteric inhibitors of wild-type and mutant forms of the BCR-ABL gene (eventually leading to development of ascinimib for treatment of Chronic Myeloid Leukemia); the first selective inhibitors of the anaplastic lymphoma kinase (ALK) gene, leading to the development of drugs such as ceritinib, which has received breakthrough designation by the United States Food and Drug Administration for the treatment of EML4-ALK expressing Non small-cell lung cancer (NSCLC); and that sphingosine-1-phosphate receptor 1 (S1P1) as the pharmacologically relevant target of the immunosuppressant drug fingolimod (FTY720) followed by the development of siponimod for the treatment of multiple sclerosis. Dr. Gray’s generalized strategy for structure-based design of inhibitors that stabilize the inactive kinase conformations (type II) has been widely adopted by the research community and has had a significant impact on the development of numerous inhibitors of tyrosine kinases currently undergoing clinical development.

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Dr. Gray’s research laboratory also developed the first T790M mutation-selective EGFR tyrosine kinase inhibitors; ATP-competitive inhibitors of mammalian target of rapamycin (mTor); Torin1 and went on to discover that rapamycin is an incomplete inhibitor of mTOR; and the first inhibitors of extracellular-signal-regulated kinase 5 (ERK5), also known as big MAP kinase 1 (BMK1); cyclin-dependent kinases (CDK7, CDK8, CDK12/13) and salt induced protein kinases (SIK) which lead to the creation of Soltego. These contributions have been recognized through numerous awards including the American Chemical Society Award for Biological Chemistry in 2011, American Association for Cancer Research Team Science Award in 2010, Damon Runyon-Rachleff Innovation Award in 2008, National Science Foundation CAREER and Outstanding Achievement awards in 2007 and 2011, respectively.  Dr. Gray has been a pioneer in the development of proximity-based therapeutics including small molecule degraders and transcription factor chemical induce proximity (TCIPs).  Nathanael has been a co-founder for numerous companies including Syros, Petra, C4, Larkspur, Matchpoint and Lighthorse Therapeutics.

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