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Contributor Information

  • Name Laurent Rigoreau
  • Institute Cancer Research Technology

Tool Details

  • Tool name: AKR1C3 inhibitor CRT0036521 Small Molecule (Tool Compound)
  • Molecular formula: C16H15NO4S
  • Tool type: Small molecules
  • Tool sub-type: Inhibitor
  • Purpose: Inhibitor
  • Description: CRT0036521 is a highly potent and selective inhibitor of the Type 5 17-?-Hydroxysteroid. A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of reverse sulfonamides showed a 12-fold preference for the R stereoisomer.
  • Research area: Cell Signaling & Signal Transduction ; Metabolism ; Neurobiology

  • For Research Use Only

Target Details

  • Target: AKR1C3

Application Details

Handling

  • Purity: 317.37 g/mol
  • Solubility:
  • Storage conditions:
  • Shipping conditions: Dry Ice

Documentation

  • Available on request

References

  •   Janieson et al. 2012. J Med.Chem. PMID: 22877157