New review: “The Role of Natural Product Chemistry in Drug Discovery: Two Decades of Progress and Perspectives” just published in the Journal of Natural Products. The review is now online and comes with the raw tabulated data in XLS format (see Supporting Information).

More than 20 years ago, I wrote a review “The Role of Natural Product Chemistry in Drug Discovery” based on a talk given at the 43^rd 2003 American Society of Pharmacognosy (ASP) meeting in New Brunswick, New Jersey. A great deal has changed since then.

In this new review, Jim La Clair and I identified and analysed 119 natural product–derived (NP-D) drugs, including 16 antibody–drug conjugates (ADCs), that received first global approval between January 2000 and September 2025. We also present six NP-D case studies and examine the representation of NP-D drugs among the top 200 brand-name medicines in 2006, 2015, and 2024.

Overall, we conclude that although NP-D drug sales have declined, agents such as dapagliflozin and empagliflozin demonstrate that blockbuster status remains achievable. While overall growth is modest, NPs continue to represent highly valuable active pharmaceutical ingredients (APIs). Importantly, substantial opportunities remain for drug-focused NP R&D, as many recently validated therapeutic targets are still underexplored for NP-D chemotypes.

📢 Our new open-access review, “Extracting Value from Marine and Microbial Natural Product Artifacts and Chemical Reactivity,” is now published in Marine Drugs.

Together with Rob Capon, we explore how chemically reactive natural products—and the artifacts they generate—are far more than analytical nuisances. When properly recognised and understood, these transformations can expose untapped regions of chemical space and create new opportunities for drug discovery and marine bioproduct development.

🔎 What is covered:

• Why artifact formation matters in natural product chemistry.
• The mechanisms (solvents, heat, pH, light, oxidation) that trigger transformations.
• Case studies showing how artifacts can provide novel insight and value including how identify “cryptic” natural products.
• Practical recommendations for recognising, controlling, and leveraging chemical reactivity in natural products research.

💡 One particularly instructive example of chemical instability is varacin (2.66, see figure), a benzopentathiepin with cytotoxic activity first reported from a Fijian ascidian Lissoclinum vareau in 1991. This striking and unusual structure attracted considerable attention at the time! A subsequent study reported varacin together with three closely related analogues, varacins A–C (2.67–2.69), from a Polycitor sp. ascidian. Notably, varacin and varacin A were shown to equilibrate with elemental sulfur (S₈, 2.70) in solution (MeOH, CH₂Cl₂, or pyridine), underscoring their chemical lability.

Related sulfur-rich systems are known to undergo light-induced sulfur radical formation, leading to sulfur ring expansion and contraction via desulfurisation and intermolecular disproportionation (see the review for further examples such as the chetomins and epithiodiketopiperazines). In the case of varacin, recombination of sulfur radicals lead to the formation of the most thermodynamically stable sulfur allotrope, S₈, in equilibrium with varacin and varacin A.

#NaturalProducts #MarineDrugs #DrugDiscovery #Chemistry #ChemicalBiology #MarineBioproducts #Research

⚠️ Nature-inspired antibiotics have been the foundation of modern medicine for over a century, but their effectiveness is under threat from drug resistance.

❓How many nature-inspired antibiotics have been approved for human use? What are their structures? Who developed and launched them, in what countries, when and for what infectious diseases? How do they work and are they still being used today?

⏳In a review publish today in Natural Product Reports, co-authored with Rob Capon, we answer all these questions and more, providing details and charting trends from the first approval of penicillin G in 1943 to 2025, backed up by over 1,000 literature citations.

👀 Some eye-opening facts:

• 217 natural product-inspired antibiotics have been used to treat human bacterial infections since 1943.
• Around 151 are still in use with around 24 only in limited use.
• 122 (81%) belong to just 5 classes: beta-lactams (71, 46%), macrolides (15, 9.9%), aminoglycosides (14, 9.3%), tetracyclines (12, 7.9%) and peptides (10, 6.6%).
• Only 3 new natural product drug classes have been approved since 2000 (daptomycin, pleuromutilin and fidaxomicin)

⏰The clock is ticking…. to learn more, follow the link.

#Antibiotics #DrugDiscovery #NatureInspired #AMR #PharmaResearch #InfectiousDiseases #NaturalProducts #MedicalResearch #GlobalHealth #ScienceCommunication

AMR is continuing to spread, but so are new models for access. Cefiderocol shows what the future of equitable antibiotics could look like.

As antimicrobial resistance continues to accelerate, particularly among carbapenem-resistant Gram-negative bacteria, cefiderocol has emerged as one of the most important new antibiotics of the past decade. Developed by Shionogi, cefiderocol is a siderophore-conjugated cephalosporin that exploits bacterial iron-uptake systems to reach the periplasm and inhibit penicillin-binding proteins. Equally important is the way it is becoming increasingly available worldwide.

🌍 While cefiderocol is currently available in Japan, the USA, the EU, and Taiwan, Shionogi’s partnership with GARDP and Orchid Pharma will reshape what equitable antibiotic access can look like.

🤝 In short, GARDP holds the licence to supply cefiderocol across 135 countries, including most low- and middle-income nations. Orchid Pharma (India) will manufacture an affordable generic version via technology transfer and a cost-plus pricing model. The goal: ensure that countries carrying the highest AMR burden aren’t the last to receive new antibiotics. More information: GARDP video and Shionogi’s website.

💊 What’s happening in Australia? An NDA for cefiderocol was accepted by the TGA in December 2024 and remains under evaluation. In April 2025, Shionogi announced an exclusive licensing agreement with Link Healthcare for development and commercialisation in Australia and New Zealand. In the interim, cefiderocol is accessible via the TGA Special Access Scheme (SAS), with 49 requests in 2023 (see 30 July FOI disclosure).

🌟 Why This Matters…

◆ Cefiderocol’s story isn’t just about a new antibiotic. It’s about building sustainable, equitable pathways to ensure life-saving AMR tools reach every region that needs them—not only high-income markets. ✔️

◆ Innovative access models like this could become the blueprint for future global preparedness against AMR. 🎯

I am pleased to announce that we (Mark S. Butler, Ian R. Henderson, Robert J. Capon and Mark A. T. Blaskovich) have been awarded the 2024 Journal of Antibiotics Ōmura Award for Reviews’ Medal for the review “Antibiotics in the clinical pipeline as of December 2022”.

It is an honour to receive an award named after Prof. Satoshi Ōmura, the 2015 Nobel Laureate and Japanese microbiologist renowned for his discovery of avermectins, which led to the development of ivermectin—a breakthrough that has transformed global health by combating parasitic diseases such as river blindness and lymphatic filariasis. His pioneering work at Kitasato University, Tokyo, exemplifies the power of natural product research in saving millions of lives.