MYCOLab Ai Logo - gold and army green

Emerging paradigms for target discovery of traditional medicines: A genome-wide pan-GPCR perspective

Summary

Traditional medicines from plants, animals, and fungi contain chemical compounds that can interact with specific proteins in our cells called G protein-coupled receptors (GPCRs). These receptors control many important body functions and are targeted by about one-third of all FDA-approved medications. This review explains how scientists are discovering new therapeutic compounds from traditional medicines by systematically screening them against the complete library of human GPCRs, using advanced techniques to identify which compounds bind to which receptors. Famous examples include morphine from poppies for pain relief and compounds from ginseng that help regulate blood sugar.

Background

Traditional medicines have served as a major source of novel therapeutics, with approximately 30% of new drugs originating from natural sources over the past two decades. G protein-coupled receptors (GPCRs) represent the largest family of membrane proteins and serve as targets for approximately one-third of FDA-approved drugs. Several compounds isolated from traditional medicines have been demonstrated to modulate GPCRs, suggesting their significant therapeutic potential.

Objective

This review contemplates prospective trends in GPCR drug discovery and proposes innovative strategies for investigating traditional medicines to identify bioactive components that either directly bind to GPCRs or indirectly modify their function. A genome-wide pan-GPCR drug discovery platform was designed to explore all-sided relations between traditional medicines and GPCRome using advanced high-throughput screening techniques.

Results

More than 600 unmodified natural products from traditional medicines have been demonstrated to modulate GPCRs, with 66% derived from medicinal plants. At least 16 GPCR-targeting drugs approved by the FDA originate from natural products or their derivatives. Key examples include alkaloid morphine targeting opioid receptors, cannabinoids targeting CB1/CB2, and peptides like exendin-4 for GLP-1R activation. Multiple indirect modulation mechanisms were identified through regulation of endogenous ligands, enzymes, and second messengers.

Conclusion

Traditional medicines represent a valuable repository for GPCR-targeting compounds with diverse chemical structures and therapeutic potential. The proposed genome-wide pan-GPCR drug discovery platform provides a systematic approach for identifying bioactive components and their GPCR targets. Further research utilizing advanced screening techniques and structural biology methods will help unlock the multi-target therapeutic properties of traditional medicines.
  • Published in:Innovation (Cambridge),
  • Study Type:Review,
  • Source: PMID: 40098666, DOI: 10.1016/j.xinn.2024.100774
Scroll to Top