Natural Product-like Fragment Library

A remarkable structural diversity and drug-likeness of molecular scaffolds identified in natural compounds provide a basis for the design of novel natural product-derived compound libraries for drug discovery [1,2]. Implementation of natural product-like frameworks into fragment-based drug discovery might benefit from using biologically validated areas of chemical space not occupied by average synthetic molecules [3,4].

Life Chemicals presents a Collection of Natural Product-like Fragments generated via the Scaffold Tree approach [5]. More than 17,000 level-two and level-three scaffolds were extracted from the Universal Natural Product Database (comprising over 220,000 structures in its current version) [6] using scaffold tree analysis. After excluding undesirable and primitive chemotypes, the remaining ca. 4,000 structures were used for substructure search within the General Fragment Collection by Life Chemicals. In addition to that, fragments derived from scaffolds showing at least 85 % similarity with the natural product-derived scaffold set mentioned above were included as well. Finally, additional structural filtering was performed.

The resulting Library comprises over 3,100 synthetic fragments similar to natural compounds as promising starting points for FBDD within an attractive chemical space. All compounds are available from stock; cherry-picking is possible.

Representative natural product-like fragments

Figure 1. Representative compounds from Natural Product-like Fragment Library

References

  1. Grabowski K.; Schneider G. Curr. Chem. Biol. 2007, 10, 115–127
  2. Rizzo S.; Waldmann H. D. Chem. Rev. 2014, 114, 4621–4639.
  3. Rodrigues T. et al. Nature Chem. 2016, 8, 531-541.
  4. Over, B. et al. Nature Chem. 2013, 5, 21–28.
  5. Schuffenhauer A. et al. J Chem Inf Model. 2007, 47, 47–58.
  6. Gu J.; Gui Y.; Chen L.; Yuan G.; Lu H.-Z.; Xu X. PLoS ONE, 2013, 8, e62839.
  7. Liu M, Quinn RJ. Expert Opin Drug Discov. 2019 Dec;14(12):1283-1295.
  8. Ertl P, Schuhmann T. J Nat Prod. 2019 May 24;82(5):1258-1263.
  9. Foley DJ et al. Chemistry. 2017 Oct 26;23(60):15227-15232.
  10. Prescher H, Koch G et al. Bioorg Med Chem. 2017 Feb 1;25(3):921-925.
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