Monya Baker in Nature:
Inside the golden-yellow spice turmeric lurks a chemical deceiver: curcumin, a molecule that is widely touted as having medicinal activity, but which also gives false signals in drug screening tests. For years, chemists have urged caution about curcumin and other compounds that can mislead naive drug hunters. Now, in an attempt to stem a continuing flow of muddled research, scientists have published the most comprehensive critical review yet of curcumin — concluding that there’s no evidence it has any specific therapeutic benefits, despite thousands of research papers and more than 120 clinical trials. The scientists hope that their report will prevent further wasted research and alert the unwary to the possibility that chemicals may often show up as ‘hits’ in drug screens, but be unlikely to yield a drug.
“Curcumin is a cautionary tale,” says Michael Walters, a medicinal chemist at the University of Minnesota in Minneapolis, and lead author of the review (K. M. Nelson et al. J. Med. Chem. http://dx.doi.org/10.1021/acs.jmedchem.6b00975; 2017), published on 11 January. Commonly used drug screens detect whether a chemical latches on to a binding site of a protein implicated in disease — a hint that it may be the starting point for a drug. But some molecules, such as curcumin, seem to show such specific activity when there is none. The molecules may fluoresce naturally, foiling attempts to use fluorescence as a signal of protein binding. They may disrupt cell membranes, duping assays that try to spot drugs targeting specific cell-membrane proteins. And they may surreptitiously degrade into other compounds that have different properties, or contain impurities that have their own biological activity. Chemists call these irritants PAINS (pan-assay interference compounds) — and curcumin is one of the worst. “Curcumin is a poster child for these promiscuous molecules that come up often in screens,” says James Inglese, who directs assay development and screening technology at the National Center for Advancing Translational Sciences in Bethesda, Maryland. “A lot of people doing this kind of work aren’t technically aware of all the issues that this thing can cause.”