Mining Natural Compounds to Target WNT Signaling: Land and Sea Tales

Area of Science:

• Biochemistry
• Pharmacology
• Drug Discovery

Background:

• WNT signaling is crucial for development, physiology, and disease, making it a key drug target.
• Despite its importance, no WNT-modulating drugs are approved, highlighting a need for new therapeutic strategies.
• Natural products possess untapped chemical diversity valuable for drug development.

Purpose of the Study:

• To explore natural products as a source for WNT signaling modulators.
• To adapt the traditional drug discovery and development pipeline for natural product-based drug discovery.
• To showcase the potential of natural compounds in developing WNT-modulating drugs.

Main Methods:

• Reviewing existing efforts in screening natural products for WNT-modulatory activity.
• Adapting the drug discovery pipeline stages (e.g., screening, lead optimization) for natural products.
• Illustrating the adapted pipeline with case studies from the authors' research.

Main Results:

• Natural products represent a powerful, largely unexplored resource for WNT signaling modulators.
• The traditional drug discovery pipeline requires modifications for effective natural product drug development.
• Case studies demonstrate the feasibility of developing natural compounds into WNT-modulating drug candidates.

Conclusions:

• Natural compounds are a promising source for novel WNT-modulating therapeutics.
• Adapting drug discovery processes is essential for harnessing the potential of natural products.
• Further research into natural products can lead to effective treatments for WNT-dependent diseases.