Background: Despite the substantial contribution of natural products to the FDA drug approval list, the
discovery of anti-cancer drugs from the huge amount of species on the planet remains looking for a needle in a haystack.
Objective: Drug-productive clusters in the phylogenetic tree are thus proposed to narrow the searching scope by
focusing on much smaller amount of species within each cluster, which enable prioritized and rational bioprospecting
for novel drug-like scaffolds. However, the way anti-cancer nature-derived drugs distribute in phylogenetic tree has
not been reported, and it is oversimplified to just focus anti-cancer drug discovery on the drug-productive clusters,
since the number of species in each cluster remains too large to be managed.
Methods: In this study, 260 anti-cancer drugs approved in the past 70 years were comprehensively analyzed by hierarchical
clustering of phylogenetic distribution.
Results: 207 out of these 260 drugs were derived from or inspired by the natural products isolated from 58 species.
Phylogenetic distribution of those drugs further revealed that nature-derived anti-cancer drugs originated mostly from
drug-productive families that tend to be clustered rather than scattered on the phylogenetic tree. Moreover, based on
their productivity, drug-producing species were categorized into productive (CPS), newly emerging (CNS) and lessproductive
(CLS). Statistical significances in druglikeness between drugs from CPS and CLS were observed, and
drugs from CNS were found to share similar drug-like properties to those from CPS.
Conclusion: This finding indicated a great raise in drug approval standard, which suggested us to focus bioprospecting
on the species yielding multiple drugs and keeping productive for long period of time.