SHANGHAI, April 30, 2014 /PRNewswire/ -- International team led by scientists at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences(SIMM) has found the detailed structure of a receptor that plays a key role in platelet activation and blood clotting. The work has implications for treatment of cardiovascular and other diseases.
In a pair of papers published by the journal Nature on May 1st, the scientists provide a detailed map of P2Y12R, a human Gi protein-coupled receptor. The antithrombotic drug target has a market of several billion U.S. dollars.
"This new work will not only deepen understanding of activation of this receptor super-family, but will also provide invaluable insight into the improvement and development of P2Y12 drugs targeting cardiovascular and other diseases," said team leader Qiang Zhao, professor at SIMM. "I was particularly proud of the high quality international collaboration between China, USA, and Germany that it took to complete this research."
The structures were solved by SIMM in collaboration with research groups from National Institutes of Health (NIH; United States), The Scripps Research Institute GPCR Network (United States), iHuman Institute of ShanghaiTech University (China) and University of Bonn (Germany).
"What we've learned from this research could pave the way for the creation of drugs with fewer limitations and health risks," said Dr. Kenneth A. Jacobson. "Our discoveries have the potential to make a significant difference in patients' lives."
Inappropriate activation of platelets can subsequently result in life-threatening conditions such as unstable angina, heart attack and stroke. Each of currently marketed P2Y12R targeting drugs has certain limitations, and efforts to develop better drugs have been impeded by poor understanding of receptor-ligand interaction.
These studies describe for the first time the structure of the P2Y12R, in complex with a full agonist and a non-nucleotide P2Y12R reversible antagonist designed by AstraZeneca. Combining the comprehensive knowledge gained from the three structures, the researchers achieved a detailed understanding of recognition of different types of drugs by the receptor.
"The research into the P2Y12 receptor gives hope for other applications," said Dr. Christa E. Muller of the University of Bonn. "Thus, the related P2Y12 receptor is, for example, involved in the metastasis of tumor cells. Here, too, new options for cancer research could arise."
SOURCE Shanghai Institute of Materia, CAS