Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs)

Bioorg Med Chem. 2011 Jun 15;19(12):3690-701. doi: 10.1016/j.bmc.2011.01.013. Epub 2011 Jan 14.

Abstract

A novel class of KAT modulators (long chain alkylidenemalonates, LoCAMs) has been identified. Variations of the alkyl chain length can change the activity profile from inhibition of both KAT3A/KAT2B (as derivative 2a) to the peculiar profile of pentadecylidenemalonate 1b, the first activator/inhibitor of histone acetyltransferases. Together with the powerful apoptotic effect (particularly notable if considering that anacardic acid and other KAT inhibitors are not cell permeable) appoint them as valuable biological tools to understand the mechanisms of lysine acetyltransferases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Histone Acetyltransferases / antagonists & inhibitors*
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / metabolism
  • Humans
  • Malonates / chemical synthesis
  • Malonates / chemistry*
  • Malonates / pharmacology*
  • U937 Cells

Substances

  • Enzyme Inhibitors
  • Malonates
  • Histone Acetyltransferases