GPCR agonists and antagonists in the clinic

Area of Science:

• Pharmacology
• Drug Discovery
• Molecular Biology

Background:

• G-protein-coupled receptors (GPCRs) are a major class of cell surface receptors involved in numerous physiological processes.
• Current therapeutic strategies primarily target a limited number of GPCRs, mainly from the rhodopsin family (e.g., biogenic amine receptors).

Purpose of the Study:

• To review current and emerging therapeutic agonists and antagonists targeting GPCRs.
• To highlight the potential of under-explored GPCRs as pharmaceutical targets.

Main Methods:

• Literature review of existing and novel GPCR-targeted therapies.
• Classification of GPCRs using the GRAFS system.
• Discussion of agonists and antagonists, focusing on new therapeutic developments.

Main Results:

• Therapies have been developed for approximately 30 GPCRs across the glutamate, rhodopsin, and secretin families.
• Advancements in technology facilitate GPCR identification and functional understanding.
• New therapies targeting specific GPCRs, including peptide-activated ones, are emerging.

Conclusions:

• Only about 4% of known GPCRs are currently targeted by therapeutics, indicating vast untapped potential.
• Numerous GPCRs represent promising targets for future pharmaceutical development.
• Further research into GPCRs can lead to novel treatments for various diseases.