AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase

J Antibiot (Tokyo). 2010 Nov;63(11):633-6. doi: 10.1038/ja.2010.51. Epub 2010 Jun 30.

Abstract

The novel immunosuppressant AS1387392 has been isolated from Acremonium sp. No. 27082. This compound showed a strong inhibitory effect against mammalian histone deacetylase and T-cell proliferation. Further, AS1387392 showed a good oral absorption, and its plasma concentration was higher than that of FR235222, an analog of AS1387392 that inhibited histone deacetylase previously reported. Given these findings, AS1387392 may represent an important new lead in developing immunosuppressant.

Publication types

  • Comparative Study

MeSH terms

  • Acremonium / chemistry*
  • Animals
  • Cell Proliferation / drug effects
  • Female
  • Fermentation
  • Histone Deacetylase Inhibitors / isolation & purification
  • Histone Deacetylase Inhibitors / pharmacokinetics
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / drug effects*
  • Histone Deacetylases / metabolism
  • Humans
  • Immunosuppressive Agents / isolation & purification
  • Immunosuppressive Agents / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacokinetics
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • AS 1387392
  • FR 235222
  • Histone Deacetylase Inhibitors
  • Immunosuppressive Agents
  • Peptides, Cyclic
  • Histone Deacetylases