S2: SBDD Approaches to PXR Binding

Structural Toxicology: SBDD Approaches to PXR Binding
Charles Leburg

Charles A. Lesburg


Merck Research Laboratories


Structures of PXR activators bound to the PXR ligand-binding domain offer an opportunity to apply structure-based methods to understand and mitigate compound-mediated induction of metabolic genes, potentially improving the metabolic profile and minimizing risk of drug-drug interactions.

Lessons learned from many complexes may buttress existing models for PXR-mediated induction.

Charles Lesburg is a Principal Scientist in the Structural Chemistry Department at Merck Research Laboratories in Boston MA USA. He obtained his doctorate at the University of Pennsylvania working for Prof. David Christianson on two major topics: the structure/function relationships of second-shell zinc-binding mutations of carbonic anhydrase II as well as early structural studies on sesquiterpene syntases. He began his professional career in 1997 at Schering-Plough Research Institute in NJ USA as a macromolecular crystallographer and has contributed to many drug discovery projects on targets including (but not limied to!) viral enzymes for antiviral therapy, kinases for oncology, fragment-based lead dicovery efforts, protein-protein interaction inhibitors, and structural methods to assess and address off-target liabilities. He also has contributed to improvements in hardware and software automation to meet the ever increasing need to be better and faster.