Researchers at the Monash University 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.
The research 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.
The 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 that 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 that they turned to their 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.
He said that their "dimmer switch" strategy worked, resulting in a molecule that protected heart cells but did not affect heart rate at all - at least in their animal models.
The research has been published in the journal Proceedings of the National Academy of Sciences (PNAS).