Featured Research

from universities, journals, and other organizations

Computational Method Points To New Uses, Unexpected Side Effects Of Already Existing Drugs

Date:
November 7, 2009
Source:
University of North Carolina School of Medicine
Summary:
Scientists have developed and experimentally tested a technique to predict new target diseases for existing drugs. The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners -- known as ligands -- of disease targets within the cell.

Bryan Roth, M.D., Ph.D.
Credit: Image courtesy of University of North Carolina School of Medicine

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.

Related Articles


The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners -- known as ligands -- of disease targets within the cell. In a study published this week in Nature, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.

"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." Roth is also a member of the UNC Lineberger Comprehensive Cancer Center.

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. Viagra, for instance, was once intended for coronary heart disease but now is used to combat erectile dysfunction. The discovery of surprising uses of developed drugs can sometimes be the result of serendipity, as unforeseen side effects emerge from clinical trials. In the past, researchers have tried to predict drug interactions by looking for chemical similarities among the possible targets of pharmaceutical compounds.

However, some drug targets which look very similar to one another bind very different ligands, and some targets that don't have any obvious similarity bind similar ligands, says Brian Shoichet, Ph.D., co-senior study author and professor of pharmaceutical chemistry at the University of California at San Francisco. "So if instead we were to organize targets by the ligands they recognize, it could reveal different patterns than traditional approaches, and illuminate new opportunities for drugs to bind to unexpected targets."

A team of researchers led by Roth and Shoichet did just that, comparing the structures of 3,365 FDA-approved and investigational drugs against the structures of hundreds of targets, defining each target by its ligands. They then honed in on thirty of the strongest predictions, validating the actual physical interactions between the drugs and targets in wet laboratory experiments.

In one of their follow-up experiments, the scientists investigated the molecular targets of the hallucinogenic substance dimethyltrytamine (DMT), which had previously been postulated to act through a site known as the sigma-1 receptor. Using the computational approach, Roth and colleagues found that DMT had a high affinity for serotonin receptors, including the binding site for LSD, another hallucinogen.

They also showed that the substance is hallucinogenic in normal mouse models but not in ones lacking the serotonin receptor. Roth says the power of their approach is 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.

"Drugs are not as selective as we once thought," said Roth, who is also a professor in the School of Pharmacy's medicinal chemistry and natural products division. "It turns out that the most non-selective drugs are frequently the most effective for complex diseases. Rather than 'magic bullets,' we need to come up with 'magic shotguns' that hit more than one molecular target at a time. We could use this computational approach to identify the drugs that hit the right targets and miss the wrong ones."

Study co-authors from UNC include Vincent Setola, research associate professor; Atheir Abbas, former graduate student; Sandra J. Hufeisen, senior research assistant; Niels H. Jensen, research associate; Michael B. Kuijer, research technician; Roberto C. Matos, research technician; Thuy B. Tran, research technician; Ryan Whaley, research technician; and Richard A. Glennon. The paper's first author is Dr. Michael Keiser, from the UCSF side of the collaboration. Also from UCSF were Drs. John Irwin, Christian Laggner and Jerome Hert, and PharmDs Kelan Thomas and Douglas Edwards.

Funding for the studies at UNC and at UCSF came from the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina School of Medicine. "Computational Method Points To New Uses, Unexpected Side Effects Of Already Existing Drugs." ScienceDaily. ScienceDaily, 7 November 2009. <www.sciencedaily.com/releases/2009/11/091104085232.htm>.
University of North Carolina School of Medicine. (2009, November 7). Computational Method Points To New Uses, Unexpected Side Effects Of Already Existing Drugs. ScienceDaily. Retrieved October 24, 2014 from www.sciencedaily.com/releases/2009/11/091104085232.htm
University of North Carolina School of Medicine. "Computational Method Points To New Uses, Unexpected Side Effects Of Already Existing Drugs." ScienceDaily. www.sciencedaily.com/releases/2009/11/091104085232.htm (accessed October 24, 2014).

Share This



More Health & Medicine News

Friday, October 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins