Theraputic agents known as allosteric ("other site") modulators take aim at targets outside of where classic drugs, and the body's own substances, normally hit selected molecules in the body.
Image: Slim Films
In Brief
- A new drug discovery approach focuses on a property known as allosterism.
- Allosteric drugs attach to biological molecules at binding sites distinct from those usually targeted
by medications. - Instead of activating or inhibiting the bound molecules, as classic drugs do, allosteric types can act more like dimmer switches and might, at times, cause fewer side effects.
- Such agents may be able to treat disorders that lack drug therapies today.
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.
Historically, scientists have developed drugs by finding molecules that mimic the behavior of our body's signaling molecules, such as hormones and neurotransmitters. The pharmaceutical doppelgangers of such endogenous substances latch onto cell-surface receptor molecules exactly where the native substances bind. If a mimic fits snugly into the binding pocket, known as the "active" site, it will activate the receptor, triggering a biochemical cascade within the cell. If the mimic has a slightly different shape, it will do the opposite, impeding the cascade. Most drugs on the market today—allergy medicines, beta blockers, antipsychotic drugs—act in one of those ways.
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2 Comments
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