New research will focus on a superfamily of protein receptors linked to various diseases.
Pharmaceutical companies Amgen, Sanofi, and Japan-based Ono Pharmaceuticals are the newest groups to jump on the university-based research bandwagon. The pharma companies announced on Oct. 28, 2014 that they will join three academic research institutes—iHuman Institute at ShanghaiTech University, Shanghai Institute of Materia Medica, and the University of Southern California—to research G-protein coupled receptors (GPCRs) and their potential role as drug targets. The initiative between the parties has been dubbed the GPCR Consortium. “The GPCR Consortium hopes to attract up to five additional industry members to achieve the initiative's goal of determining structures of 200 of the 826 known human GPCRs, prioritized in disease areas that initially include diabetes, cancer, and mental disorders,” according to a press release.
GPCRs are membrane proteins that undergo conformational changes when their receptors are activated. They sense signaling molecules, such as neurotransmitters or hormones, and are proteins central to cell communications. They mediate the cellular response to these signals on an extracellular level, and these signals trigger a cascade of biochemical activity inside of the cell.
The research will focus on understanding the structure of GPCRs by analyzing high-resolution pictures of the proteins. It is thought that knowing what these structures look like and how they work mechanistically could help researchers design more selective compounds.
"The academic groups involved in the consortium have published both the first human GPCR structure and the majority of GPCR structure-function and discovery data, including structures from the major classes of the GPCR family," said Michael Hanson, PhD, president of the GPCR Consortium, in a press release. "The importance of this family of proteins for human health cannot be overstated as communication with the environment is a hallmark of higher functioning organisms, and GPCRs play a central role in this process."
At least 30% of all drugs target GPCRs, according to an article in Nature. The beta-blocker, for example, works by attaching to GPCRs and blocking their reaction to the hormone adrenalin. Antihistamines also target this class of receptor. GPCRs are being investigated for the treatment of Alzheimer’s disease and are already used in drugs to treat HIV and schizophrenia. Heptares, who is developing the first fully selective muscarinic M1 receptor agonist for the treatment of Alzheimer’s disease, discovered the target using a GPCR structure-based drug design platform.