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New Research Finds Novel Uses for Old Drugs

A recent article in C&EN reports that scientists at the University of North Carolina at Chapel Hill School of Medicine and the University of California, San Francisco have developed and experimentally tested a technique to predict new target diseases for existing drugs. The team, led by Bryan L. Roth and Brian K. Shoichet, developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring ligands of disease targets within cells. In their study, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.

Many of the most successful drugs on the market today are being prescribed for ailments that are quite different from the ones they were originally designed to treat since many drugs have been found to bind to multiple targets. Sometimes these interactions lead to new uses for well established drugs. At other times, they may cause harmful side effects. Either way, knowing about these interactions allows for better use of drugs.

In the new method, drug receptors are not defined by structure or sequence but by the ligands that bind to them. This approach differs from structure-based approaches which usually use a receptor’s crystal structure as a starting point.

“This approach uncovered interactions between drugs and targets that we never could have predicted simply by looking at the chemical structures,” said senior study author Bryan Roth, M.D., Ph.D., professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC. “We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing.”

By using a modified version of an already established algorithm used to search gene-sequence databases, compounds were screened against a database of targets, asking how much the compounds looked like the ligands. The team compared 3,665 approved or investigational drugs with hundreds of targets which were defined by their ligands. The researchers predicted thousands of unanticipated interactions and experimentally tested 30 of them. Of these 30, they confirmed 23 of the interactions.

In one case, the team found  that Rescriptor, which inhibits the enzyme HIV reverse transcriptase, also inhibited the histamine H4 receptor. The scientists have linked Rescriptor binding to histamine H4 at physiologically relevant concentrations to some of the painful side effects that the drug has. In another example, the antidepressant Prozac, whose primary target is the serotonin transporter, bound the beta-1 adrenerfic receptor, a G-protein-coupled receptor (GPCR) that usually binds such compounds as epinephrine and norepinephrine.

Roth states that the power of their approach is that it can be used to uncover the real targets of pharmaceutical compounds quickly and efficiently, and will probably lead to a greater understanding of the many molecular targets of each drug. Consequently, this new method will be an important step forward for chemists to design drugs that act on multiple targets.

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Can traveling on airlines with liquids soon be possible?

confiscated items-wDepending on how frequently you travel, you may or may not have experienced the many inconveniences of going through airport security. Considering that I travel approximately 2200 miles to get to Villanova, I fall into the former category. One of these inconveniences is the restriction of carrying liquids onto commercial airlines. There are several techniques (e.g., nuclear magnetic spectroscopy) that could be employed to screen liquids as to whether or not they could be used as potential explosives. However, these techniques are usually too expensive or require too much time to be implemented in airports. Fortunately, a BBC article is reporting that German scientists have developed a quick technique that could be used to test for potentially dangerous liquids, thus making the ban on carrying liquids through airport security unnecessary. The proposed technique is called Hilbert spectroscopy and involves using a very wide spectrum of light to identify liquids that could be mixed to form an explosive or that have already been mixed. When baggage is X-rayed in airport security, measurements are usually confused by the packaging and other items inside the bag. The new technique manages to get around this problem by using the wider range of frequencies.

“The trick, they say, is to use a “nanoelectronic” device known as a Josephson junction. This allows the frequencies of light reflected from a sample to be quickly added up. This in turn provides a chemical “fingerprint” of the item being analyzed.”

The key advantage of using the Josephson junction is that it spans the low and high frequency ranges covered by significantly more expensive devices. The scientists responsible for the new technique have conceded that further developments are necessary to refine their approach but they are confident that the technique can be applied to security screening. If this technique is implemented, frequent travelers may be spared one less inconvenience. I, for one, would very much like to see this technique widely adopted.

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