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:5/25/2016)... ... May 25, 2016 , ... Dr. Travis Schwarz is an experienced dentist ... Road, O’Fallon, MO 63366. He serves patients of all ages with a full menu ... Schwarz’s success is reflected in the superior patient reviews that he has consistently earned ...
(Date:5/25/2016)... ... May 25, 2016 , ... DKT International, one of the ... is pleased to release their 2015 global impact data. In 2015, DKT served ... maternal deaths and 3.8 million unsafe abortions across 21 countries worldwide. , ...
(Date:5/25/2016)... ... May 25, 2016 , ... ... its annual Medical and Prescription Drug survey , an employee benefits ... survey, which was conducted in December 2015, indicates that employers are turning to ...
(Date:5/25/2016)... CA (PRWEB) , ... May 25, 2016 , ... "FCPX ... the quality of your footage," said Christina Austin - CEO of Pixel Film Studios. ... editors can quickly and easily add stylish color grades to their footage. A LUT ...
(Date:5/25/2016)... Atlanta GA (PRWEB) , ... May 25, 2016 ... ... workplace solutions builder, has announced that it will join America's leading engineers at ... will be held at the Georgia World Congress Center. , Engineers, speakers ...
Breaking Medicine News(10 mins):
(Date:5/23/2016)... Non-invasive diagnostic test realizes the ... ,Technology to be presented at Yissum’s booth, at IATI-BIOMED ... Company of the Hebrew University of Jerusalem announced ... Aurum Ventures MKI, the technology investment arm of Morris ... approach for early detection of multiple diseases by analyzing ...
(Date:5/23/2016)... -- Gamida Cell, a leader in cellular ... orphan genetic diseases, announced today it has been awarded ... Israel Innovation Authority (formerly the Office of the Chief ... The mission of the Israel Innovation Authority is to ... and technology, while stimulating economic growth. The ...
(Date:5/23/2016)... STAMFORD, Conn. , May 23, 2016 /PRNewswire/ ... Company has entered into an agreement with Egalet ... various patent claims. As part of the agreement ... rights, and will enable all three companies to ... abuse-deterrent properties. "This agreement reflects the ...
Breaking Medicine Technology: