Natural products: Are we close to the end?

Natural products have historically played a central role in drug discovery and development, but the re-isolation of known scaffolds is reported to increasingly hamper efforts to mine natural products chemical space for novel bioactive molecules. Despite the promise offered by orthogonal discovery strategies such as genome mining and the exploration of new taxonomic space, examination of the literature implies that most natural products being published today bear significant structural similarities to existing scaffolds.

This empirical observation inspired us to systematically explore the state of natural products discovery from the standpoint of both discovery rates and structural novelty. Using a database containing all microbial and marine-derived natural products we determined the Tanimoto structure similarity scores for all database members. We then used these data to examine a number of questions in this area, including: the rates of novel compound discovery over time, the effects of exploring novel source organisms on molecular diversity, and the projected rate of novel discovery for future natural products efforts. Results from these analyses will be presented, along with a perspective on the implications of these findings for future natural products discovery strategies.