NCI’s natural product library: A 326,656 compound update!

Dear All,

I wrote in 2018 about National Cancer Institute’s Natural Products Branch (NPB) and its program for Natural Product Discovery (NPNPD) as a resource for antimicrobial discovery. In brief, it’s a global collection of natural products that is available as a library of semi-pure natural product samples that comes pre-platted in 384-well plates. The deep idea behind this program is that while natural products have historically been a productive source of new active chemotypes, natural product samples have more recently been only a small percentage of samples tested for antimicrobial activity. Aside: If you are not familiar with the idea of Natural Products, please see either this Wikipedia page for a quick overview or this review paper for a deeper dive that includes more detailed discussions of the challenges of working with natural products.

The new item for today is a paper by Martínez-Fructuoso et al. (ACS Infect. Dis. 2023, 9:1245–1256) detailing a joint effort by the National Cancer Institute and the National Institute of Allergy and Infectious Diseases in which 326,656 fractions were screened against three bacteria (S. aureus and two strains of E. coli) and one strain of a fungus (C. albicans) for the ability to directly inhibit growth of these organisms. 

This screen identified >3000 fractions with whole cell activity vs. these bacteria and/or fungi. To prove that these results were potentially intriguing, the team then explored 75 of these fractions in further detail. Encouragingly, at least some of the fractions had selective activity vs. bacteria or fungi, but not against both. This sort of selectivity is a very good thing … molecules that kill everything bacteria AND fungi will often kill everything else, including human cells. Arsenic-based compounds have been used successfully (well, sort of … see this discussion of the infection-related twist in the movie Out of Africa), but we try to avoid going to such extremes in the modern era!

Does this mean these are drugs? No, almost certainly not! But, the possibility of investigating them as starting points would be entirely rational. Before these could be considered as more than just hits but as possible lead compounds, you would want to see data on at least some of the properties discussed in the compound checklist given in the Instructions to Authors for Antimicrobial Agents and Chemotherapy. You might also enjoy our recent 4-part series on AI-based discovery in which we consider the idea of Chemicals vs. Drugs at length.

Excitingly, the whole list of active samples is being made publicly available to encourage further research on the vast majority of active samples identified. The hope is that researchers will take up the isolation and structure elucidation of additional antimicrobial chemotypes identified in this study. The NCI Natural Products Branch can provide crude extracts of up to 1 gram to qualified researchers (when supplies are permitting) to enable such purification projects. 

Interested? If so, the senior authors of the paper (Tanja Grkovic and Barry R. O’Keefe) can be reached at tanja.grkovic@nih.gov and okeefeba@mail.nih.gov. Happy drug hunting! 

All best wishes and with thanks to the teams at NCI and NIAID, –jr

John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Operating Partner, Advent Life Sciences. Follow me on Twitter: @JohnRex_NewAbx. See past newsletters and subscribe for the future: https://13.43.35.2/blog/. All opinions are my own.

Current funding opportunities (most current list is here)

  • The AMR Action Fund is now open to proposals for funding of Phase 2 / Phase 3 antibacterial therapeutics. Per its charter, the fund prioritizes investment in treatments that address a pathogen prioritized by the WHO, the CDC and/or other public health entities that: (i) are novel (e.g., absence of known cross-resistance, novel targets, new chemical classes, or new mechanisms of action); and/or (ii) have significant differentiated clinical utility (e.g., differentiated innovation that provides clinical value versus standard of care to prescribers and patients, such as safety/tolerability, oral formulation, different spectrum of activity); and (iii) reduce patient mortality. It is also expected that such agents would have the potential to strongly address the likely requirements for delinked Pull incentives such as the UK (NHS England) subscription pilot and the PASTEUR Act in the US. Submit queries to contact@amractionfund.com.
  • BARDA’s long-running BAA-18-100-SOL-00003 offers support for both antibacterial and antifungal agents. This BAA has offered 4 deadlines/year since 2018 … check the most current amendment for details.
  • INCATE (Incubator for Antibacterial Therapies in Europe) is an early-stage funding vehicle supporting innovation vs. drug-resistant bacterial infections. The fund provides advice, community, and non-dilutive funding (€10k in Stage I and up to €250k in Stage II) to support early-stage ventures in creating the evidence and building the team needed to get next-level funding. Details and contacts on their website (https://www.incate.net/).
  • These things aren’t sources of funds but would help you develop funding applications
    • AiCuris’ AiCubator offers incubator support to very early stage projects. Read more about it here.
    • The Global AMR R&D Hub’s dynamic dashboard (link) summarizes the global clinical development pipeline, incentives for AMR R&D, and investors/investments in AMR R&D.
    • Diagnostic developers would find valuable guidance in this 6-part series on in vitro diagnostic (IVD) development. Sponsored by CARB-XC-CAMP, and FIND, it pulls together real-life insights into a succinct set of tutorials.
  • In addition to the lists provided by the Global AMR R&D Hub, you might also be interested in my most current lists of R&D incentives (link) and priority pathogens (link).


Upcoming meetings of interest to the AMR community (most current list is here):

  • 3-5 Jul 2023 (Tours, France): 9th Symposium on Antimicrobial Resistance in Animals and the Environment (ARAE). Sponsored by INRAE (French National Research Institute for Agriculture, Food, and Environment, itself a merger of merger of INRA, the French National Institute for Agricultural Research, and IRSTEA, the French National Research Institute of Science and Technology for the Environment and Agriculture), this conference has been running since 2005. Go here for details.
  • 4-6 Aug 2023 (Bangkok, Thailand): The regional Medical Mycology Training Network Conference by ISHAM’s Asia Fungal Working Group is set to feature both hands-on workshops and clinical sessions for all those managing and working with invasive fungal infections. Go here for details. 
  • 19-22 Sep 2023 (Boston, USA): ASM-ESCMID Joint Conference on Drug Development to Meet the Challenge of Antimicrobial Resistance. This is an excellent development focused meeting … highly recommended! Go here for details and to register. 
  • 7-15 Oct 2023 (residential, Annecy, France): ICARe, the Interdisciplinary Course on Antibiotics and Resistance. Now in its 7th year, this course is a deep-dive into the world of antibiotic development. Intense, rigorous, and HIGHLY recommended. Seats are always limited … apply sooner rather than later! Go here for details.
  • 11-15 Oct 2023 (Boston, USA): IDWeek 2023, the annual meeting of the Infectious Diseases Society of America. Go here for details and to register. 
  • 20-23 Oct 2023 (Athens, Greece): 11th TIMM (Trends in Medical Mycology). Go here for details.
  • 6-7 Feb 2024 (online): Antimicrobial Chemotherapy Conference. This is an annual, free of charge conference that is co-organized by GARDP and the British Society for Antimicrobial Chemotherapy (BSAC). Details to follow — for now, just mark your calendar.
  • 27-30 April 2024 (Barcelona, Spain): 34th ECCMID, the annual meeting of the European Society for Clinical Microbiology and Infectious Diseases. Go here for details.

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