Department of Mathematics

Applied Mathematics

  •  Meihua Tu, Medicine Design, Pfizer Inc.
  •  The role of water molecules in Ketohexokinase (KHK) inhibitor design
  •  12/02/2019
  •  10:00 AM - 11:00 AM
  •  C304 Wells Hall

Increased fructose consumption and its subsequent metabolism have been implicated in hepatic steatosis, dyslipidemia, obesity, and insulin resistance in humans. Since ketohexokinase (KHK) is the principal enzyme responsible for fructose metabolism, inhibition of KHK may ameliorate non-​alcoholic fatty liver disease (NAFLD) and non-​alcoholic steatohepatitis (NASH) by decreasing fructose conversion to fructose-​1-​phosphate. Initial low MW hits were identified by fragment screening. A combination of parallel synthesis and structure-​based drug design yielded a clinic candidate, currently in clinic trials. This presentation will focus on computational techniques that have been applied in the optimization of lead compounds. In particular, how water molecule energy profile in the binding pocket was used to guide compound design. Our successful fragment-​to-​candidate story will demonstrate the power of combining structure-​based drug design with parallel chem.

 

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Department of Mathematics
Michigan State University
619 Red Cedar Road
C212 Wells Hall
East Lansing, MI 48824

Phone: (517) 353-0844
Fax: (517) 432-1562

College of Natural Science