Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification

Irina Vetter, Wayne Clarence Hodgson, David J Adams, Peter McIntyre

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

3 Citations (Scopus)

Abstract

The study of venoms is driven by a desire to understand the structural and functional diversity of venom components and, in particular, the mechanism of action of lethal components from medically important animals such as scorpions, spiders, stonefish and snakes. Initially, target-driven venom screens were rare. Bioassays in whole animals or isolated tissues were used to characterise behavioural and physiological parameters of venoms. Molecular fractionation of venom components required more specific bioassays to identify components based on pharmacological or physiological responses of anaesthetised whole animals or tissue preparations such as skeletal muscle, smooth muscle and isolated blood vessels. These assays can be extremely informative because they often measure an integrated tissue response that cannot be seen in more defined cellular assays. Despite this, the convenience and sensitivity of modern biochemical and cellular bioassays means that they are now widely used to characterise venom components. Such assays have the advantage that they can be miniaturised and performed in multiwell plates. Together with the development of high-throughput platforms such as the FLIPR and automated electrophysiology devices, these miniaturised assays have facilitated the high-throughput screening of venoms components against enzymes, receptors and ion channels, many of which are validated drug targets. These assay platforms are likely to be a major driver that will significantly expedite future venoms-based drug discovery efforts. The aim of this chapter is to summarise the various assays that are being used to identify and determine the mode of action of drug leads derived from animal venoms.
Original languageEnglish
Title of host publicationVenoms to Drugs : Venom as a Source for the Development of Human Therapeutics
EditorsGlenn F King
Place of PublicationUK
PublisherThe Royal Society of Chemistry
Pages97 - 128
Number of pages32
Edition1st
ISBN (Print)9781849736633
DOIs
Publication statusPublished - 2015

Cite this

Vetter, I., Hodgson, W. C., Adams, D. J., & McIntyre, P. (2015). Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification. In G. F. King (Ed.), Venoms to Drugs : Venom as a Source for the Development of Human Therapeutics (1st ed., pp. 97 - 128). UK: The Royal Society of Chemistry. https://doi.org/10.1039/9781849737876-00097
Vetter, Irina ; Hodgson, Wayne Clarence ; Adams, David J ; McIntyre, Peter. / Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification. Venoms to Drugs : Venom as a Source for the Development of Human Therapeutics. editor / Glenn F King. 1st. ed. UK : The Royal Society of Chemistry, 2015. pp. 97 - 128
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Vetter, I, Hodgson, WC, Adams, DJ & McIntyre, P 2015, Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification. in GF King (ed.), Venoms to Drugs : Venom as a Source for the Development of Human Therapeutics. 1st edn, The Royal Society of Chemistry, UK, pp. 97 - 128. https://doi.org/10.1039/9781849737876-00097

Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification. / Vetter, Irina; Hodgson, Wayne Clarence; Adams, David J; McIntyre, Peter.

Venoms to Drugs : Venom as a Source for the Development of Human Therapeutics. ed. / Glenn F King. 1st. ed. UK : The Royal Society of Chemistry, 2015. p. 97 - 128.

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

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AB - The study of venoms is driven by a desire to understand the structural and functional diversity of venom components and, in particular, the mechanism of action of lethal components from medically important animals such as scorpions, spiders, stonefish and snakes. Initially, target-driven venom screens were rare. Bioassays in whole animals or isolated tissues were used to characterise behavioural and physiological parameters of venoms. Molecular fractionation of venom components required more specific bioassays to identify components based on pharmacological or physiological responses of anaesthetised whole animals or tissue preparations such as skeletal muscle, smooth muscle and isolated blood vessels. These assays can be extremely informative because they often measure an integrated tissue response that cannot be seen in more defined cellular assays. Despite this, the convenience and sensitivity of modern biochemical and cellular bioassays means that they are now widely used to characterise venom components. Such assays have the advantage that they can be miniaturised and performed in multiwell plates. Together with the development of high-throughput platforms such as the FLIPR and automated electrophysiology devices, these miniaturised assays have facilitated the high-throughput screening of venoms components against enzymes, receptors and ion channels, many of which are validated drug targets. These assay platforms are likely to be a major driver that will significantly expedite future venoms-based drug discovery efforts. The aim of this chapter is to summarise the various assays that are being used to identify and determine the mode of action of drug leads derived from animal venoms.

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Vetter I, Hodgson WC, Adams DJ, McIntyre P. Venoms-Based Drug Discovery: Bioassays, Electrophysiology, High-Throughput Screens and Target Identification. In King GF, editor, Venoms to Drugs : Venom as a Source for the Development of Human Therapeutics. 1st ed. UK: The Royal Society of Chemistry. 2015. p. 97 - 128 https://doi.org/10.1039/9781849737876-00097