NaturalProductLed

NaturalProductLed, or natural product-led discovery, is an approach in drug discovery that prioritizes natural products as the starting point for identifying and optimizing lead compounds. It emphasizes chemical entities derived from living organisms, including plants, microorganisms, and marine sources, rather than relying primarily on synthetic libraries.

Key steps typically include isolation of compounds from natural sources, activity screening, and dereplication to avoid rediscovery of known substances, followed by structure elucidation. Lead optimization may involve semi-synthesis or total synthesis, supported by medicinal chemistry to improve pharmacokinetic properties, efficacy, and safety. Development often includes preclinical evaluation and considerations of supply and scalability.

Advantages of natural product leads include access to structurally diverse scaffolds and evolved biological interactions that can yield novel mechanisms of action not commonly found in synthetic libraries. The approach can reveal targets and pathways that complement other discovery strategies.

Challenges include limited and variable supply, complex and stereochemically rich structures that are difficult to optimize, dereplication and intellectual property considerations, reproducibility, and regulatory hurdles. Integrating modern techniques such as high-throughput isolation, advanced analytical methods, and data-driven dereplication can mitigate some issues but requires multidisciplinary collaboration.

Recent trends involve genome mining, metagenomics, and biosynthetic engineering to access new natural products, alongside advances in analytical chemistry and synthetic biology. NaturalProductLed is viewed as a complementary strategy to target-based and purely synthetic discovery, applicable in both academic and industrial settings.