Tricyclodecan-9-yl-xanthogenate (D609) mechanism of actions: a mini-review of literature

Neurochem Res. 2012 Apr;37(4):671-9. doi: 10.1007/s11064-011-0659-z. Epub 2011 Nov 22.

Abstract

Tricyclodecan-9-yl-xanthogenate (D609) is known for its antiviral and antitumor properties. D609 actions are widely attributed to inhibiting phosphatidylcholine (PC)-specific phospholipase C (PC-PLC). D609 also inhibits sphingomyelin synthase (SMS). PC-PLC and/or SMS inhibition will affect lipid second messengers 1,2-diacylglycerol (DAG) and/or ceramide. Evidence indicates either PC-PLC and/or SMS inhibition affected the cell cycle and arrested proliferation, and stimulated differentiation in various in vitro and in vivo studies. Xanthogenate compounds are also potent antioxidants and D609 reduced Aß-induced toxicity, attributed to its antioxidant properties. Zn²⁺ is necessary for PC-PLC enzymatic activity; inhibition by D609 might be attributed to its Zn²⁺ chelation. D609 has also been proposed to inhibit acidic sphingomyelinase or down-regulate hypoxia inducible factor-1α; however these are down-stream events related to PC-PLC inhibition. Characterization of the mammalian PC-PLC is limited to inhibition of enzymatic activity (frequently measured using Amplex red assay with bacterial PC-PLC as a standard). The mammalian PC-PLC has not been cloned; sequenced and structural information is unavailable. D609 showed promise in cancer studies, reduced atherosclerotic plaques (inhibition of PC-PLC) and cerebral infarction after stroke (PC-PLC or SMS). D609 actions as an antagonist to pro-inflammatory cytokines have been attributed to PC-PLC. The purpose of this review is to comprehensively evaluate the literature and summarize the findings and relevance to cell cycle and CNS pathologies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology*
  • Bridged-Ring Compounds / therapeutic use
  • Cell Cycle / drug effects*
  • Cell Cycle / physiology
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / enzymology
  • Humans
  • Norbornanes
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
  • Sphingomyelin Phosphodiesterase / metabolism
  • Thiocarbamates
  • Thiones / chemistry
  • Thiones / pharmacology*
  • Thiones / therapeutic use
  • Type C Phospholipases / antagonists & inhibitors*
  • Type C Phospholipases / metabolism

Substances

  • Antioxidants
  • Bridged-Ring Compounds
  • Norbornanes
  • Thiocarbamates
  • Thiones
  • tricyclodecane-9-yl-xanthogenate
  • Type C Phospholipases
  • Sphingomyelin Phosphodiesterase