CP-225,917 and CP-263,114, novel Ras farnesylation inhibitors from an unidentified fungus. I. Taxonomy, fermentation, isolation, and biochemical properties

J Antibiot (Tokyo). 1997 Jan;50(1):1-7. doi: 10.7164/antibiotics.50.1.

Abstract

During the course of our screening for squalene synthase inhibitors and Ras farnesylation inhibitors, a novel fungal culture was discovered to produce two structurally unique compounds, CP-225,917 and CP-263,114, as well as zaragozic acid A (squalestatin I). The two compounds are characterized by a bicyclo[4.3.1]dec-1,6-diene core plus two extended alkyl chains. CP-225,917 and CP-263,114 inhibit Ras farnesyl transferase from rat brain with IC50 values of 6 microM and 20 microM, respectively. CP-225,917 inhibits squalene synthase with an IC50 value of 43 microM and CP-263,114 with an IC50 of 160 microM. The producing organism, though not fully classified, exhibits the characteristics of a sterile Phoma species.

MeSH terms

  • Alkyl and Aryl Transferases*
  • Animals
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Farnesyl-Diphosphate Farnesyltransferase / antagonists & inhibitors
  • Fermentation*
  • Fungi / classification*
  • Fungi / metabolism
  • Maleic Anhydrides / isolation & purification*
  • Maleic Anhydrides / pharmacology
  • Rats
  • Transferases / antagonists & inhibitors*

Substances

  • CP 225917
  • CP 263114
  • Enzyme Inhibitors
  • Maleic Anhydrides
  • Transferases
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • Farnesyl-Diphosphate Farnesyltransferase