G Protein-Coupled Receptors (GPCRs)

• Researchers have shown that the regulation of G Protein-Coupled Receptors (GPCRs) by new drugs can be simpler than generally thought — it can be mediated by engaging only the end of the receptor, which is called the tail of the receptor.

About G protein coupled receptor?

• G protein-coupled receptors (GPCRs) are a large family of proteins  located on the surface of all cells in the body, particularly in the brain. They sense stimuli such as light, smells, hormones and neurotransmitters, and initiate cellular responses to these cues.
• GPCR signalling controls virtually every physiological process in the body, making these receptors the targets of many current drugs treating conditions like pain, hypertension, schizophrenia and asthma.
• Nearly 50% of prescription drugs currently available in the market for the treatment of blood pressure, heart failure, diabetes, obesity, cancer and many other human diseases target GPCR receptors. All these drugs bind to their respective receptors and either activate or stop their signalling.
• There are over 375 GPCRs encoded in the human genome, of which 225 have known ligands and 150 are orphan targets.
• Drug discovery targeting GPCRs remains challenging, however. In contrast to classes of soluble protein drug targets, such as kinases and proteases, the understanding of GPCRs has been severely hampered by the lack of structural and mechanistic knowledge and an understanding of how compounds interact with them. This has resulted in a general lack of quality GPCR drug leads advancing through pharma pipelines, high failure rates and no successful NCEs to multiple validated high-value targets.
• The overriding problem is that GPCRs are very unstable and lose their highly organised structure and activity when taken out of the cell membrane.
   

By: Vishal