Featured Research

from universities, journals, and other organizations

Potential heart attack drug without side effects under development

Date:
March 11, 2014
Source:
Monash University
Summary:
A team of scientists combining molecular pharmacology and medicinal chemistry reveal new insights into a specific protein belonging to the family of G protein-coupled receptors (GPCRs). After successfully combining two molecules, they are a step closer to creating a brand new class of drug that is more targeted and could possess minimal side effects.

Melbourne scientists are a step closer to creating a new drug to stop a heart attack in its tracks and reduce the damage caused, without any side effects.

Related Articles


The Monash University research, published today in the journal, Proceedings of the National Academy of Sciences, USA (PNAS), offers new hope to thousands of people who experience heart attacks and heart failure -- one of the major causes of death worldwide.

Professors Arthur Christopoulos and Peter Scammells from the Monash Institute of Pharmaceutical Sciences (MIPS) led a team of scientists combining molecular pharmacology and medicinal chemistry to reveal new insights into a specific protein belonging to the family of G protein-coupled receptors (GPCRs). After successfully combining two molecules, they are a step closer to creating a brand new class of drug that is more targeted and could possess minimal side effects.

GPCRs play a role in virtually every biological process and most diseases, including, cardiovascular disease, obesity and diabetes, neuropsychiatric disorder, inflammation and cancer. Almost half of all current medications available use GPCRs to achieve their therapeutic effect.

Current GPCR drugs work either by fully activating or completely blocking receptors, treating the protein like a simple "on-off" switch. This new research discovered alternative recognition sites on GPCRs that can be targeted by drugs to fine-tune the behavior of the protein, basically converting the "on-off" switch into a "dimmer switch."

Professor Christopoulos said it was this insight that enabled the new breakthrough.

"When a heart attack strikes, heart cells die because of a lack of oxygen and nutrients. But even more damage is caused when the blood rushes back to the heart cells due to the release of inflammatory chemicals and damaging free radicals," Professor Christopoulos said.

Currently, drugs to minimize damage to the heart activate the adenosine A1 receptor, a GPCR found in the heart. However, a major issue in activating the A1 receptor also slows down the heart, and too much activation can stop the heart.

"Correct dosage has been a serious challenge in clinical trials for A1 receptor drugs. The consequences are serious; a dosage that is too high can stop the heart from beating. Too low, and the drug fails to prevent cell damage. Getting this balance right has been a big problem," Professor Scammells said.

Professor Christopoulos said the Monash study focused on finding new ways to activate the protein, to achieve the beneficial effects (protection) without the side effects (slowing the heart).

"We turned to our knowledge of alternative recognition sites on the A1 receptor and specifically designed a new class of molecule that contained two active components linked together, one binding to the main site on the receptor for activation, and another binding to the alternative site for fine-tuning of the activity. Our "dimmer switch" strategy worked, resulting in a molecule that protected heart cells but did not affect heart rate at all -- at least in our animal models," Professor Christopoulos said.

"The beauty of this protein is that if you activate it effectively, you minimise the heart attack and protect the heart cells, and that's something that's never been done before."

The findings will inform the next phase of the research to develop a new drug that could potentially be made available for use by clinicians and emergency paramedics.


Story Source:

The above story is based on materials provided by Monash University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Celine Valant, Lauren T. May, Luigi Aurelio, Chung Hui Chuo, Paul J. White, Jo-Anne Baltos, Patrick M. Sexton, Peter J. Scammells, and Arthur Christopoulos. Separation of on-target efficacy from adverse effects through rational design of a bitopic adenosine receptor agonist. PNAS, March 2014 DOI: 10.1073/pnas.1320962111

Cite This Page:

Monash University. "Potential heart attack drug without side effects under development." ScienceDaily. ScienceDaily, 11 March 2014. <www.sciencedaily.com/releases/2014/03/140311104919.htm>.
Monash University. (2014, March 11). Potential heart attack drug without side effects under development. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2014/03/140311104919.htm
Monash University. "Potential heart attack drug without side effects under development." ScienceDaily. www.sciencedaily.com/releases/2014/03/140311104919.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Christmas Kissing Good for Health

Christmas Kissing Good for Health

Reuters - Innovations Video Online (Dec. 22, 2014) Scientists in Amsterdam say couples transfer tens of millions of microbes when they kiss, encouraging healthy exposure to bacteria. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
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