3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site

Bioorg Med Chem Lett. 2003 Jun 16;13(12):2055-8. doi: 10.1016/s0960-894x(03)00310-x.

Abstract

3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.

MeSH terms

  • Adenosine Monophosphate / metabolism*
  • Allosteric Site
  • Animals
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology
  • Fructose-Bisphosphatase / antagonists & inhibitors*
  • Fructose-Bisphosphatase / metabolism
  • Humans
  • Indoles / chemistry
  • Indoles / metabolism*
  • Indoles / pharmacology*
  • Models, Molecular
  • Propionates / chemistry
  • Propionates / metabolism*
  • Propionates / pharmacology*
  • Rabbits
  • Rats
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Swine

Substances

  • 2-carboxy-4,6-dichloro-(1H)-indole-3-propanoic acid
  • Enzyme Inhibitors
  • Indoles
  • Propionates
  • Recombinant Proteins
  • Adenosine Monophosphate
  • Fructose-Bisphosphatase