GPCR Frequently Asked Questions
What are GPCRs?
GPCRs - shorthand for G protein-coupled receptors - are transmembrane proteins on a cell's surface that can interact with both the environment outside and inside the cell. As such, they play a crucial role in receiving chemical signals from other cells and, in response, activating certain cellular responses.
Molecules called ligands bind to the portion of the GPCR on the outside of the cell, activating the GPCR by allowing it to bind with a G protein and setting off a series of events within the cell. Much drug development today is focused on finding chemicals that affect the ability of the ligands to bind with the GPCR, thereby either inhibiting or accelerating the cellular process.
Why are GPCRs important in human health?
GPCRs play a crucial role in many diverse disease processes. The receptors have been linked to regulation of behavior and mood through GPCRs found in the brain, inflammation through receptors in the immune system, and metabolic processes, among others.
What drugs target GPCRs?
A high percentage of today's prescription drugs target one or more GPCRs, and we believe that approved GPCR-based drugs target about 30% of the known non-sensory GPCRs.
How does Arena's Constitutively Activated Receptor Technology (CART) improve screening?
We have invented a technique that activates GPCRs without the presence of a receptor's natural ligand, a process called Constitutively Activated Receptor Technology (CART). Drug-like compounds can then be screened against the active GPCR, allowing researchers to spot potential drugs that interact with the receptor. We have found that CART can be applied broadly to both orphan and known GPCRs. In addition, the technology allows our researchers to find compounds that inhibit activation as well as those that activate the GPCR.
What are the benefits of examining "orphan" GPCRs?
Orphan GPCRs have no known ligand. Examining orphan GPCRs expands the number of receptors that can be screened. GPCRs are crucial to many biological functions. Analysis of a greater number of GPCRs increases the odds of finding important and novel treatments.
How does the Melanophore technology improve screening?
Our Melanophore technology is a broadly applicable, high-throughput screen for GPCRs that uses frog skin cells to visually signal when GPCRs couple with their G protein or proteins, allowing researchers to assess when a receptor has been inhibited or stimulated.
We believe our Melanophore technology is also well suited for studies of orphan receptors, where little is known about the way it couples with G proteins. We also believe Melanophore technology provides us with a robust, reproducible, high-throughput and low-cost means for identifying and optimizing GPCR agonists, antagonists and inverse agonists, and is sensitive enough to detect the constitutive activity of many GPCRs.