Navigation Links
Study paves way to design drugs aimed at multiple protein targets at once
Date:12/12/2012

CHAPEL HILL, N.C. An international research collaboration led by scientists at the University of North Carolina School of Medicine and the University of Dundee, in the U.K., have developed a way to efficiently and effectively make designer drugs that hit multiple protein targets at once.

This accomplishment, described in the Dec. 13, 2012 issue of the journal Nature, may prove invaluable for developing drugs to treat many common human diseases such as diabetes, high blood pressure, obesity, cancer, schizophrenia, and bi-polar disorder.

These disorders are called complex diseases because each have a number of genetic and non-genetic influences that determine susceptibility, i.e., whether someone will get the disease or not.

"In terms of the genetics of schizophrenia we know there are likely hundreds of different genes that can influence the risk for disease and, because of that, there's likely no single gene and no one drug target that will be useful for treating it, like other common complex diseases," said study co-leader, Brian L. Roth, MD, PhD, Michael J. Hooker Distinguished Professor of Pharmacology in the UNC School of Medicine, professor in the Division of Chemical Biology and Medicinal Chemistry in the UNC Eshelman School of Pharmacy, and director of the National Institute of Mental Health Psychoactive Drug Screening Program.

In complex neuropsychiatric conditions, infectious diseases and cancer, Roth points out that for the past 20 years drug design has been selectively aimed at a single molecular target, but because these are complex diseases, the drugs are often ineffective and thus many never reach the market.

Moreover, a drug that acts on a single targeted protein may interact with many other proteins. These undesired interactions frequently cause toxicity and adverse effects.

"And so the realization has been that perhaps one way forward is to make drugs that hit collections of drug targets simultaneously. This paper provides a way to do that," Roth said.

The new way involves automated drug design by computer that takes advantage of large databases of drug-target interactions. The latter have been made public through Roth's lab at UNC and through other resources.

Basically, the researchers, also co-led by Andrew L. Hopkins, PhD in the Division of Biological Chemistry and Drug Discovery, College of Life Sciences, at the University of Dundee, in Scotland, used the power of computational chemistry to design drug compounds that were then synthesized by chemists, tested in experimental assays and validated in mouse models of human disease.

The study team experimentally tested 800 drug-target predictions of the computationally designed compounds; of these, 75 percent were confirmed in test-tube (in vitro) experiments.

Drug to target engagement also was confirmed in animal models of human disease. In a mouse model of attention deficit hyperactivity disorder (ADHD), mice missing a particular dopamine receptor engage in recurrent aberrant behaviors similar to what is seen in ADHD: distractibility and novelty seeking. "We created a compound that was predicted to prevent those recurrent behaviors and it worked quite well," Roth said.

The researchers then tested the compound in another mouse model where a particular enzyme for a brain neuropeptide is missing. Distractibility and novelty seeking also are behavioral features in these animals. And the drug had the same effect in those mice.

The new drug design process includes ensuring that compounds enter the brain by crossing the blood-brain barrier. These, too, were tested successfully in live animals.

According to Roth, pharmaceutical company chemists had suggested that the objective of a drug hitting multiple targets simultaneously is impossible and unlikely to succeed. "Here we show how to efficiently and effectively make designer drugs that can do that."


'/>"/>

Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina Health Care
Source:Eurekalert  

Related medicine news :

1. Targeted micro-bubbles detect artery inflammation, MU study finds
2. Study Finds New SARS-Like Virus Spread Through Bats, Pigs
3. Junk Food Taxes Pay Off, Study Finds
4. Brain Changes Continue After Childs Concussion: Study
5. Even Light Smoking Boosts Womens Risk of Sudden Heart Death: Study
6. Primary Care Doctors Meet Needs of Diabetics, Study Says
7. Avastin Shows No Benefit for Earlier Colon Cancer: Study
8. Regular Exercise May Add Years to Life, Study Finds
9. Coffee May Lower Risk of Death From Mouth Cancer: Study
10. RSNA: New Study Finds Brain Angioplasty and Stents Safe and Effective for Stroke Patients
11. Salmonella spreads by targeting cells in our gut, study shows
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study paves way to design drugs aimed at multiple protein targets at once
(Date:2/9/2016)... ... ... The Journal of Pain Research has published the commentary “ Terminology ... author Dr John F. Peppin says “Terminology matters, yet little attention has been paid ... ‘Chronic cancer pain’ and ‘chronic non-cancer pain’ are replete in the literature; however, the ...
(Date:2/9/2016)... ... February 09, 2016 , ... ZipHearing.com is ... to affordable hearing aids , increase industry transparency, and promote awareness of ... States. , “For the average consumer, the hearing aid industry is esoteric and ...
(Date:2/9/2016)... ... ... Two renowned photographers, Robert Caplin (New York, NY) and Peter Lockley (Denver, ... 2016, hosted by Four Seasons Resort Maui at Wailea as part of the luxury ... the Maui Photo Expedition workshop will once again consist of on-location shoots, ...
(Date:2/9/2016)... ... 09, 2016 , ... i2i Systems, an early innovator and developer of population ... the latest KLAS report, Population Health Management 2015: How Far Can Your Vendor Take ... health management (PHM). The latest KLAS Report, leveraging over 200 user interviews, shines ...
(Date:2/8/2016)... ... , ... CURE Media Group , the nation’s leading digital and print ... Awards event , which will annually honor individuals making heroic contributions in the field ... MM Heroes Awards nomination process is officially open through February 17 for patients, ...
Breaking Medicine News(10 mins):
(Date:2/9/2016)... LONDON , Feb. 9, 2016 The ... in 2014, and it is expected to grow with ... types, the glass prefilled syringes segment dominated the global ... --> --> The global ... significant rate, due to increasing geriatric population, increasing demand ...
(Date:2/9/2016)... , Feb. 9, 2016 The new report "Global Blood Monitoring ... Acuity Business Research & Consulting group reveals that global market for ... million in 2014 and expected to grow to US$ 24,830.1 million ... North America , Europe ... , Middle-East and Africa ...
(Date:2/9/2016)... 9, 2016  Increasingly, health care professionals are enhancing ... with wireless technology. With the Vios Monitoring System from ... and remotely detect problems before they become serious by ... environments. the United States . ... . --> The Vios Monitoring System ...
Breaking Medicine Technology: