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Therapeutic Potentials of Recently Identified PLD Inhibitors

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Abstract:

The signaling enzyme Phospholipase D (PLD) has been implicated in numerous cell biological processes, including Ras activation, cell spreading, stress fiber formation, chemotaxis, and vesicular trafficking during neurotransmitter and hormonal release. These observations have been mostly obtained from cell culture experiments using a primary alcohol to inhibit PLD activity or by modulating endogenous expression levels of the PLD1 and PLD2 isoforms. Since modulating PLD levels can have non-specific long-term effects and alcohols have been described to cause PLD-independent deleterious effects, the identification of potent specific small molecule PLD inhibitors is an important advance for the field. In this review, I will highlight the recent identification and characterization of chemical PLD inhibitors and describe their potential therapeutic interest in the treatment of human brain diseases/disorders and cancer metastasis.





Keywords: Phospholipase D; cancer; cognition; immunity; inhibitor

Document Type: Research Article

Publication date: September 1, 2010

More about this publication?
  • Current Chemical Biology aims to publish full-length and mini reviews on exciting new developments at the chemistry-biology interface, covering topics relating to Chemical Synthesis, Science at Chemistry-Biology Interface and Chemical Mechanisms of Biological Systems.

    Current Chemical Biology covers the following areas: Chemical Synthesis (Syntheses of biologically important macromolecules including proteins, polypeptides, oligonucleotides, oligosaccharides etc.; Asymmetric synthesis; Combinatorial synthesis; Diversity-oriented synthesis; Template-directed synthesis; Biomimetic synthesis; Solid phase biomolecular synthesis; Synthesis of small biomolecules: amino acids, peptides, lipids, carbohydrates and nucleosides; and Natural product synthesis).

    Science at Chemistry-Biology Interface (Chemical informatics; Macromolecular catalysts and receptors; Enzymatic synthesis; Biosynthetic engineering; Combinatorial biosynthesis; Plant cell based chemistry; Bacterial and viral cell based chemistry; Chemistry of cellular processes in plants/animals; Receptor chemistry; Cell signaling chemistry; Drug design through understanding of disease processes; Synthetic biology; New high throughput screening techniques; Small molecular array fabrication; Chemical genomics; Chemical and biological approaches to carbohydrates proteins and nucleic acids design; Chemical and biological regulation of biosynthetic pathways; and Unnatural biomolecular analogs).
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