G-Protein-Coupled Receptors are the Most Diverse Type of Receptors in the Human Body

Friday 21 October 2011, Amsterdam

G-Protein-Coupled Receptors are the Most Diverse Type of Receptors in the Human Body

A superfamily of diverse transmembrane receptors, GPCRs help in the activation of cellular responses by interacting with molecules outside the cell. These molecules are known as ligands. The cellular responses are activated through a system of signaling pathways, called as signal transduction pathways. Human genome sequencing has helped us to understand the importance of these diverse classes of receptors, with about 1,000 sequences identified to be GPCRs. About 400 GPCRs bind with endogenous ligands; however such ligands have not been discovered for about 33% of all GPCR targets, thus emphasizing on the potential these receptors have as targets for future drug discovery.
 

Novel Research Methods are Being Employed to Identify and Develop Products that Target GPCRs More Effectively

The understanding of GPCR biology was limited for a very long time, although researchers were successful in identifying many GPCR targets using genomic approaches. However, there was no real understanding of the receptor structure-function relationship, and how different signaling molecules activated these receptors. Hence, the goal was to find the endogenous and/or exogenous ligands that paired with each GPCR, which could help the discovery of new avenues in therapy and de-orphanization of GPCRs. However, there are still more than 100 orphan GPCRs for which ligands have not yet been identified. This coupled with the fact that only about 30% of the 800 odd GPCRs have been targeted so far by currently marketed medicines leads to the conclusion that GPCR research has immense potential to bring out new therapies. Basic research advances concerning receptor X-ray structures, allosteric interactions and functional selectivity have opened the way for further exploitation of this large and diverse class of targets.


Research and Development Efforts in the Area of GPCRs will be Concentrated, Especially on De-Orphanization of Orphan GPCRs

Some of the new GPCRs discovered, especially those discovered through sequence homology, had one basic problem in that the endogenous ligands that bind to these receptors could not be identified. Hence, such receptors without any endogenous ligands were termed orphan GPCRs. One would think that functional activity of orphan GPCRs would be questioned as there are no known ligands that bind to these receptors, however expression of these orphan receptors in many different species accounts for their functional activity. Discovery of ligands that target orphan GPCRs is proving to be an extremely challenging task for researchers and for pharmaceutical and biotechnology companies all over the world. With the number of new molecules that get approval from the regulatory authorities falling drastically, coupled with the arrival of a patent cliff for the next four to five years, researchers are looking at the super-family of GPCRs with more interest than ever before. One of the most important segments of GPCR research concentrates on de-orphanizing GPCRs, identifying unknown ligands and establishing functional activity for orphan receptors.
 

Pipeline Analysis of Molecules Reveals the Central Nervous System, Oncology and Cardiovascular System to be the Most Targeted Therapeutic Classes

There are many programs looking at the role of GPCRs in obesity, the role of GPCRs in pain states, and in controlling tumorigenesis. A large number of CNS diseases involve GPCRs, ranging from depression to neurodegenerative diseases such as Alzheimer’s disease, and they are therefore looked at in both the peripheral and the central nervous system. Many research papers defining receptor pharmacology use the brain for ligand-binding experiments. Modern research labs continue to study receptor pharmacology in brain tissue. There may be a preponderance of work on GPCRs in CNS because of this history, but there are lots of opportunities to progress GPCR therapeutics in many other areas.


About this new market study:
This report provides a scientific understanding of GPCRs and details the novel research methods being employed in the research of new targets and molecules that can be more effective in treating many indications. A special note on Orphan GPCRs and ways to de-orphanize them is followed by a detailed pipeline analysis to understand the therapeutic classes and indications that are being targeted through GPCRs. The report provides an in-depth analysis of the competitive landscape, including the profiling of top companies and licensing agreements involving GPCR molecules and platform technologies.