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January 8, 2014
A Tool Compound's New Personality
Here's a paper that may require some recalibration in the existing literature. It reports that a widely-used tool compound LY294002, known as an inhibitor of the PI3 kinases, is also a bromodomain ligand. There seems little doubt that some of its cellular effects, depending on the assay conditions, could be due to this mode of action, rather than its kinase activity. Putting "LY294002" into a PubMed search gives you, as of this morning, 7075 hits, so surely some of these results have been muddied up a bit.
PI3K and the BRD bromodomain family are, as you'd figure, structurally unrelated, but that doesn't stop things like this from happening. Time and again, tool compounds that have been accepted as acting on System A have turned out to also hit System B, and when system Z gets discovered, turn out to hit that one, too. The point is, there are a *lot* of ligand binding sites out there, and to assume that a given compound only hits the one that you know about is unwarranted. Now, at the same time, very little progress gets made if you assume that there are no tool compounds at all, so the only thing to do is proceed alertly, and be ready to revise your conclusion. Which is how we're supposed to be working, anyway, right?
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