Using venoms to uncover new targets in drug discovery

A range of drugs used in modern medicine are derived from animal venoms, and Steve Trim from Venomtech discusses how natural selection has made venoms particularly useful tools for uncovering new targets in drug discovery…

Finding a specific and selective tool compound quickly in the life of a project can be as frustrating as having an imperial bolt and a box of metric spanners – nothing quite does the job. This is nothing new, and the scale of the challenge is all too obvious to the experienced drug discovery teams. If serendipity is on your side you will find a published tool available commercially, or a diversity set screen will deliver hits, but often this is not the case. The decision about where to go next can be like deciding which direction to sail the pirate ship for the next bounty. Understanding the biology of the target will always lead the search for tools and ultimately drugs, but understanding the biology of potential tools will also be of great use.

Evolution has honed a complex web of biological pathways, and although there is now a vast amount of information at our fingertips, we still don’t know all the details of these intricate interactions. Within an organism, signalling occurs largely through proteins and peptides binding to receptor proteins, but many smaller molecules are also produced naturally that act through their own receptors and channels. Engineering xenobiotics to modulate these complex systems takes a long time and has a huge cost.

In the natural world, this is also the case. Plants have been locked into a predator-prey battle with animals ever since the dawn of the animal kingdom. In order to defend their tissues against damage from hungry animals, plants have evolved a wide range of chemical and physical defences, although obviously it is their chemical defences that are of interest to drug discovery. The earliest use of plants for medicine probably came from observing unusual effects from eating them. Some traditional cures have since been found to contain good pharmaceutical actives.

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