Chemistry Seminar: Mutant-selective allosteric inhibitors for mutant EGFR lung cancer

Mutant-selective allosteric inhibitors for mutant EGFR lung cancer

Dr. David Heppner
Assistant Professor, Department of Chemistry
College at Buffalo

Dr. Heppner will present on overcoming drug resistance mechanisms using mutant-selective EFGR inhibitors to combat lung cancer.

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Abstract:
Activating mutations within the EGFR kinase domain are major drivers of non-small cell lung cancer and often predict for successful treatment with EGFR tyrosine kinase inhibitors. However, drug resistance eventually emerges often with acquisition of additional mutations within the EGFR kinase. To overcome these resistance mechanisms, a series of mutant-selective EGFR inhibitors were discovered and found to bind an allosteric pocket that is accessible due to the presence of the activating and drug resistant mutations. Inspired by ATP-site inhibitors, molecules that bind both the ATP and allosteric sites were generated through structure-guided drug design and optimized for selectivity for EGFR mutations and their ability to kill cancer cells. As current efforts focus on evolving these molecules for deployment in clinical trials, these studies offer key examples of how searching for and designing allosteric inhibitors can generate highly selective next-generation cancer treatments.

Speaker Bio:
Dr. David Heppner is Assistant Professor of Chemistry at SUNY Buffalo. Joining the Faculty at UB in the fall of 2020. From 2017-2020, Dr. Heppner was a Post-doctoral research Fellow at the Dana Farber Cancer Institute in the Harvard medical School and from 2014 -2017 he was an NIH Postdoctoral Fellow at the Larner college of Medicine at the University of Vermont. He took is Ph.D. in Chemistry at Stanford University in 2014 The Heppner lab at UB applies an integrative approach through a combination of medicinal chemistry, biochemistry, cellular and molecular biology, biophysics, and structural biology to discover and design novel therapeutics and molecular tools for biological applications. Research is directed to understanding protein structural and mechanistic characteristics that control biochemical processes important in cancer biology and other diseases. Current areas of interest include: discovery and design of first-in-class small molecule inhibitors as targeted therapies in cancer and other diseases, structural and functional understanding of post-translational modifications at protein cysteine residues, and pharmacology and structural biology of metalloproteins and redox enzymes.

Intended Audience:
Undergraduates, graduates, and experts. Those with interest in the topic.