Creating and Screening Natural Product Libraries

Overview

Journal Nat Prod Rep

Publisher Royal Society of Chemistry

Date 2020 Mar 19

PMID 32186299

Citations 51

Authors

Brice A P Wilson

Christopher C Thornburg

Curtis J Henrich

Tanja Grkovic

Barry R OKeefe

Affiliations

Soon will be listed here.

Abstract

Covering: up to 2020The National Cancer Institute of the United States (NCI) has initiated a Cancer Moonshot program entitled the NCI Program for Natural Product Discovery. As part of this effort, the NCI is producing a library of 1 000 000 partially purified natural product fractions which are being plated into 384-well plates and provided to the research community free of charge. As the first 326 000 of these fractions have now been made available, this review seeks to describe the general methods used to collect organisms, extract those organisms, and create a prefractionated library. Importantly, this review also details both cell-based and cell-free bioassay methods and the adaptations necessary to those methods to productively screen natural product libraries. Finally, this review briefly describes post-screen dereplication and compound purification and scale up procedures which can efficiently identify active compounds and produce sufficient quantities of natural products for further pre-clinical development.

Citing Articles

Repurposing brucine as a chemopreventive agent in mammary gland carcinoma: Regulating lactate transport through MCT-4.

Zaidi A, Kumar A, Kumar R, Singh J, Yadav S, Sonkar A Toxicol Rep. 2025; 14:101902.

PMID: 39897398 PMC: 11787605. DOI: 10.1016/j.toxrep.2025.101902.

Nature's magic: how natural products work hand in hand with mitochondria to treat stroke.

Cheng L, Lv S, Wei C, Li S, Liu H, Chen Y Front Pharmacol. 2025; 15():1434948.

PMID: 39840113 PMC: 11747497. DOI: 10.3389/fphar.2024.1434948.

Chemical biology research in RIKEN NPDepo aimed at agricultural applications.

Osada H Proc Jpn Acad Ser B Phys Biol Sci. 2025; 101(1):8-31.

PMID: 39805590 PMC: 11808203. DOI: 10.2183/pjab.101.003.

CRISPR-Cas9-based genome-editing technologies in engineering bacteria for the production of plant-derived terpenoids.

Sun X, Zhang H, Jia Y, Li J, Jia M Eng Microbiol. 2024; 4(3):100154.

PMID: 39629108 PMC: 11611024. DOI: 10.1016/j.engmic.2024.100154.

Isolation, biosynthesis, and biological activity of rubromycins derived from actinomycetes.

Lin P, Li X, Xin Y, Li H, Li G, Lou H Eng Microbiol. 2024; 2(3):100039.

PMID: 39629028 PMC: 11611039. DOI: 10.1016/j.engmic.2022.100039.

References

Yang J, Sanchez L, Rath C, Liu X, Boudreau P, Bruns N . Molecular networking as a dereplication strategy. J Nat Prod. 2013; 76(9):1686-99. PMC: 3936340. DOI: 10.1021/np400413s. View

Patridge E, Gareiss P, Kinch M, Hoyer D . An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today. 2015; 21(2):204-7. DOI: 10.1016/j.drudis.2015.01.009. View

Makley L, Gestwicki J . Expanding the number of 'druggable' targets: non-enzymes and protein-protein interactions. Chem Biol Drug Des. 2012; 81(1):22-32. PMC: 3531880. DOI: 10.1111/cbdd.12066. View

Perez-Moreno G, Cantizani J, Sanchez-Carrasco P, Ruiz-Perez L, Martin J, El Aouad N . Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products. PLoS One. 2016; 11(1):e0145812. PMC: 4703298. DOI: 10.1371/journal.pone.0145812. View

Annang F, Perez-Moreno G, Garcia-Hernandez R, Cordon-Obras C, Martin J, Tormo J . High-throughput screening platform for natural product-based drug discovery against 3 neglected tropical diseases: human African trypanosomiasis, leishmaniasis, and Chagas disease. J Biomol Screen. 2014; 20(1):82-91. DOI: 10.1177/1087057114555846. View

Bugni T, Richards B, Bhoite L, Cimbora D, Harper M, Ireland C . Marine natural product libraries for high-throughput screening and rapid drug discovery. J Nat Prod. 2008; 71(6):1095-8. PMC: 2533854. DOI: 10.1021/np800184g. View

Bermingham A, Price E, Marchand C, Chergui A, Naumova A, Whitson E . Identification of Natural Products That Inhibit the Catalytic Function of Human Tyrosyl-DNA Phosphodiesterase (TDP1). SLAS Discov. 2017; 22(9):1093-1105. PMC: 7900901. DOI: 10.1177/2472555217717200. View

Coussens N, Braisted J, Peryea T, Sittampalam G, Simeonov A, Hall M . Small-Molecule Screens: A Gateway to Cancer Therapeutic Agents with Case Studies of Food and Drug Administration-Approved Drugs. Pharmacol Rev. 2017; 69(4):479-496. PMC: 5612261. DOI: 10.1124/pr.117.013755. View

Goey A, Chau C, Sissung T, Cook K, Venzon D, Castro A . Screening and Biological Effects of Marine Pyrroloiminoquinone Alkaloids: Potential Inhibitors of the HIF-1α/p300 Interaction. J Nat Prod. 2016; 79(5):1267-75. PMC: 6323635. DOI: 10.1021/acs.jnatprod.5b00846. View

10.

Baell J, Holloway G . New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J Med Chem. 2010; 53(7):2719-40. DOI: 10.1021/jm901137j. View

11.

Tran T, Wilson B, Henrich C, Staudt L, Krumpe L, Smith E . Secondary Metabolites from the Fungus Dictyosporium sp. and Their MALT1 Inhibitory Activities. J Nat Prod. 2019; 82(1):154-162. PMC: 7462088. DOI: 10.1021/acs.jnatprod.8b00871. View

12.

Coma I, Bandyopadhyay D, Diez E, Ruiz E, Teresa de Los Frailes M, Colmenarejo G . Mining Natural-Products Screening Data for Target-Class Chemical Motifs. J Biomol Screen. 2014; 19(5):749-57. DOI: 10.1177/1087057114521463. View

13.

Newman D, Cragg G . Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod. 2016; 79(3):629-61. DOI: 10.1021/acs.jnatprod.5b01055. View

14.

Gerry C, Schreiber S . Chemical probes and drug leads from advances in synthetic planning and methodology. Nat Rev Drug Discov. 2018; 17(5):333-352. PMC: 6707071. DOI: 10.1038/nrd.2018.53. View

15.

Sarwar M, Zhang H, Tsang S . Perspectives of Plant Natural Products in Inhibition of Cancer Invasion and Metastasis by Regulating Multiple Signaling Pathways. Curr Med Chem. 2017; 25(38):5057-5087. DOI: 10.2174/0929867324666170918123413. View

16.

Gaestel M, Kotlyarov A, Kracht M . Targeting innate immunity protein kinase signalling in inflammation. Nat Rev Drug Discov. 2009; 8(6):480-99. DOI: 10.1038/nrd2829. View

17.

Camp D, Davis R, Campitelli M, Ebdon J, Quinn R . Drug-like properties: guiding principles for the design of natural product libraries. J Nat Prod. 2011; 75(1):72-81. DOI: 10.1021/np200687v. View

18.

Perola E . An analysis of the binding efficiencies of drugs and their leads in successful drug discovery programs. J Med Chem. 2010; 53(7):2986-97. DOI: 10.1021/jm100118x. View

19.

Grkovic T, Pouwer R, Vial M, Gambini L, Noel A, Hooper J . NMR fingerprints of the drug-like natural-product space identify iotrochotazine A: a chemical probe to study Parkinson's disease. Angew Chem Int Ed Engl. 2014; 53(24):6070-4. PMC: 4298794. DOI: 10.1002/anie.201402239. View

20.

Xu Y, Brooks A, Wijeratne E, Henrich C, Tewary P, Sayers T . 17β-Hydroxywithanolides as Sensitizers of Renal Carcinoma Cells to Tumor Necrosis Factor-α Related Apoptosis Inducing Ligand (TRAIL) Mediated Apoptosis: Structure-Activity Relationships. J Med Chem. 2017; 60(7):3039-3051. PMC: 6986374. DOI: 10.1021/acs.jmedchem.7b00069. View