Thursday April 24, 6:30-9:30pm

SC10: Introduction to Targeted Covalent Inhibitors*

Brion W. Murray, Ph.D., Research Fellow, Pfizer Oncology
Christoph Zapf, Ph.D., Principal Scientist, Worldwide Medicinal Chemistry, Pfizer Research Labs


Panelist: Erik Verner, Ph.D., Director, Chemistry, Principia Biopharma

Covalent inhibitors of kinases have re-emerged as a drug design strategy due to more examples of their safety and efficacy in patients. Covalent inhibitors have the advantage of increased selectivity and longer action of duration but there are still important issues about their design and application that need to be better understood. This course will cover practical as well as theoretical issues that a medicinal chemist needs to keep in mind in developing covalent inhibitors.

  • Overview of covalent drugs, irreversible and reversible inhibitors including recent clinical examples
  • Biochemical analysis of covalent inhibitors
  • Design considerations for targeted covalent inhibitors
  • De-risking covalent inhibitors
  • Mechanism of drug resistance
  • Panel discussion/Q&A

Recent publication by Brion Murray related to covalent kinase inhibitors:
Covalent EGFR Inhibitor Analysis.pdf 

Instructor Biographies

Brion MurrayBrion W. Murray, Ph.D., Research Fellow, Pfizer Oncology

Dr. Brion Muray is a researcher, leader, and mentor with over 28 years of research experience. He received a B.S in Chemistry from the University of North Carolina, Chapel Hill and a Ph.D. in Biochemistry from the University of Maryland. Brion’s post-doctoral studies were in the laboratory of Chi-Huey Wong at The Scripps Research Institute. Brion has worked at the biotech companies Signal Pharmaceuticals (now Celgene) and Agouron (now Pfizer). Currently he is a Research Fellow in the Pfizer Oncology Research Unit where he has developed a biochemical framework for understanding and describing irreversible covalent drugs (PNAS2014). Brion has also made scientific discoveries that resulted in 40 publications and 16 patents. He discovered mechanisms of receptor tyrosine kinase regulation (redox control, conformation regulation; co-discovered an inhibitor binding mode for receptor tyrosine kinases; discovered mechanisms of receptor tyrosine kinase drug resistance; co-discovered the JNK inhibitor SP-600125 and co-discovered B kinases. Brion led the team that identified the first p21-activatedI kinase drug and was a member of the teams that discovered two FDA-approved drugs (axitinib, crizotinib).

Christoph ZapfChristoph Zapf, Ph.D., Principal Scientist, Worldwide Medicinal Chemistry, Pfizer Research Labs

Dr. Christoph Zapf is a Principal Scientist in the Biotherapeutics Chemistry department within Worldwide Medicinal Chemistry at Pfizer. One of his main tasks as a Design Chemist is to conceive and deliver new small molecule drug candidates that have the highest chance of survival in the development phase and clinical trials. Christoph received his master’s degree in chemistry in Germany before moving to San Diego in 1998 to pursue his graduate education under the guidance of Prof Murray Goodman at UCSD. After receiving his Ph.D. degree in 2003 he moved to Princeton University where he carried out postdoctoral studies in Total Synthesis in the laboratories of Prof Erik Sorensen. Christoph launched his career in 2005 in the Chemical and Screening Sciences department at Wyeth in Pearl River, NY and was folded into Pfizer’s Worldwide Medicinal Chemistry group following the merger in 2009. Christoph subsequently relocated to Cambridge, Massachusetts where he has worked as a design chemist since 2011. Over the years Christoph has worked on a range of pharmaceutical targets spanning from oncology to antiviral to most recently anti-inflammatory agents.

*Separate registration is required