High throughput receptor-based virtual screening under ZINC database, synthesis, and biological evaluation of ketol-acid reductoisomerase inhibitors

Chem Biol Drug Des. 2010 Feb;75(2):228-32. doi: 10.1111/j.1747-0285.2009.00924.x. Epub 2009 Dec 17.


Ketol-acid reductoisomerase (KARI; EC catalyzes the second common step in branched-chain amino acid biosynthesis. This enzyme is an important target for drug design. Based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate (IpOHA) complex, we have carried out high throughput receptor-based virtual screening of the ZINC/drug like database (2 000 000 compounds) to look for novel inhibitors of KARI for the first time. Some novel compounds were found to inhibit rice KARI in vitro among 15 procured compounds. This method can provide useful information for further design and discovery of KARI inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Databases, Factual
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • High-Throughput Screening Assays*
  • Ketol-Acid Reductoisomerase / antagonists & inhibitors*
  • Ketol-Acid Reductoisomerase / metabolism
  • Protein Binding


  • Enzyme Inhibitors
  • Ketol-Acid Reductoisomerase