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A Biochemical Way to Reduce Drug Side Effects?

Despite what the overcrowded, overpriced shelves of your pharmacy might suggest, pharmaceutical companies struggle to find new drugs these days. The low-hanging fruit is long gone, and the main discovery method that served so well in past decades is generating far fewer hits today. But a fresh strategy, focused on a property called allosterism, is now invigorating many investigators. Some predict it will revolutionize drug discovery and could deliver treatments for diseases that so far remain intractable.

Thanks to a few serendipitous discoveries arising from an upgrade in technology, pharmaceutical companies are now moving beyond mimicry drugs. They are on the hunt for agents that interact with receptor regions that are geographically distinct from where a body’s chemicals bind. These allosteric drugs, as they are called—allosteric means “other site”—can interact with unique domains on receptor subtypes, thus limiting side effects by affecting only a narrow set of receptors possessing those domains. And the new agents are not mere on-off switches; they can have nuanced effects, ramping up or down the activity of a signaling pathway as needed.

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