USING a database of molecular interactions may help to prevent drugs鈥� side effects by predicting how they will interact with the body鈥檚 receptors. It might even suggest new target diseases for existing drugs.
Most drugs work by binding to a receptor or other molecule on cells, triggering a biochemical change. But many bind to other receptors too, producing side effects that only show up after tests in animals or people.
Thinking about how to predict these unintended targets, , a computational chemist at the University of California, San Francisco, and colleagues reasoned that if a drug鈥檚 shape resembles that of another molecule known to bind to a certain target, then the drug may bind to that target too.
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Potential targets
Using published databases of interactions between small molecules, or 鈥渓igands鈥�, and potential targets, they used software to search for similarities in chemical structure between ligands and 3665 drugs either in use or under development. This yielded a list of nearly 4000 previously unknown potential targets.
Some of these new targets might explain known side effects. The software predicted that the anti-nausea drug should also bind to a receptor that contributes to cardiac arrhythmia 鈥� one of the drug鈥檚 side effects. Others point to new uses: the antihistamine should block a receptor involved in Alzheimer鈥檚 disease.
Experiments are still needed to prove that these drugs really do bind to the predicted targets, and that this has a biological effect.
The approach provides a way to identify potential targets, and might help drug designers find drugs that hit several targets at once, says Andrew Hopkins, a pharmacologist at the University of Dundee, UK. 鈥淚t is often by not being selective that drugs exert their effects.鈥�
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