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Binding timenot just affinitygains stature in drug design
npg 201 5 Nature America, Inc. All rights reserved.
In the early twentieth century, German scientist Paul Ehrlich coined a phrase that has since served as a framework on which pharmaceutical companies develop drugs: corpora non agunt nisi fixataa substance will not work unless it is bound to its target. As such, drug developers have selected the drugs that bind most tightly to their targets in preclinical studies to use in early-stage clinical trials. Paradoxically, many of the drug candidates brought into the clinic fail to have much of an effect in patients. Scientists started looking at binding time more closely in the late 1990s and early 2000s. In 2006, chemist Robert Copeland put forth the term drug-target residence time to explain why drugs lack efficacy in humans. He argued that its not only how tightly a drug binds to its target that matters, but rather, how long the drug stays bound to its target. (Nat. Rev. Drug Discov. 5, 730739, 2006).
Ever since Copeland detailed the residence time idea almost a decade ago, scientists have attempted to use the concept of binding time to predict in vivo efficacy. Although these previous attempts yielded insights, Copeland says that a new paper offers an improved model for the residence time concept. Whats new and really important about [this study] is that [the researchers] have developed an elegant, mathematical model for incorporating residence time and kinetic variables into a single equation, Copeland says. There have been cruder models before, but this...