SC8: GPCR STRUCTURE-BASED DRUG DISCOVERY

WEDNESDAY, SEPTEMBER 18 | 7:00 - 9:30 PM

The high-resolution structures of G protein-coupled receptors (GPCRs) determined by X-ray crystallography and recently by cryo-EM are rapidly impacting the pharmaceutical industry. This course will review the structural biology concepts and tools that have enabled successful GPCR structural determination. We will also examine how the elucidated structures have informed our current understanding of GPCR function. Examples will be provided of how GPCR structural information is guiding rational design of subtype selectivity and functional selectivity for small molecules. Perspectives on current gaps in GPCR structure-based drug design will be provided at the end to stimulate deep thinking and discussion on how to overcome these hurdles.

Topics to be Discussed:

  • Overview of methodologies and biophysical advances that facilitated GPCR crystallography 
  • Recent cryo-EM structures of GPCR complexes
  • Review of high profile, drug discovery-significant GPCR structures
  • Impact of elucidated structures on GPCR-targeted drug design
  • Challenges in GPCR structure-based drug design
  • NOTE: CHI will email course registrants one month before the course requesting them to email the name of their 'favorite' GPCR to the instructor to help her customize the course

Instructor:

Wu_HuixianHuixian Wu, PhD, Principal Scientist, Structural and Molecular Sciences, Discovery Sciences, Pfizer, Inc.

Dr. Huixian Wu received her PhD in Structural Biology and Chemistry from the Scripps Research Institute (La Jolla, CA) in the laboratory of Prof. Raymond C. Stevens. While in Stevens lab, Dr. Wu focused on G protein-coupled receptor (GPCR) crystallography where she determined the crystal structures of several important human GPCRs, including the k-opioid receptor, metabotropic glutamate receptor, and smoothened receptor. After completing her PhD, Dr. Wu joined Prof. Stuart L. Schreiber’s laboratory in the Broad Institute of Harvard and MIT (Cambridge, MA) for postdoctoral research, working on structure-based drug development (SBDD) targeting inflammatory bowel diseases. Currently, Dr. Wu is a Principal Scientist leading a Crystallography lab at Pfizer (Groton, CT). Her lab is supporting SBDD of diverse therapeutic targets across multiple disease areas in Pfizer.

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