Clues for future bioprospecting:from the clustered patterns of species origins of nature-derived drugs
Many drugs are nature-derived.Low drug productivity has renewed interest in natural products as drug discovery sources.Nature-derived drugs are composed of dozens of molecular scaffolds generated by specific secondary metabolite gene clusters in selected species.It can be hypothesized that drug-like structures are likely distributed in selective species-groups.We analyzed species-origins of 939 approved and 369 clinical-trial drugs with respect to those of 119 preclinical drugs and 19,721 bioactive natural products.In contrast to scattered distribution of bioactive natural products,these drugs are clustered into 144 out of 6763 known species-families in nature,with 80% and 67% of the approved and clinical-trial drugs concentrated in 17 and 30 drug-prolific families respectively.Four lines of evidences from historical drug data,13,548 marine natural products,767 medicinal plants and 19,721 bioactive natural products suggest that drugs are mostly derived from pre-existing drug-productive families.Drug-productive clusters expand slowly by conventional technologies.Lack of drug outside drug-productive families is not necessarily due to under-exploration and late-exploration by conventional technologies.New technologies that explore cryptic gene-clusters,pathways,interspecies crosstalk and high-throughput fermentation enable the discovery of novel natural products.Their potential impact on drug productivity and distribution patterns of drug-productive families is yet to be revealed.
朱峰 蒋宇扬 陈宇综
重庆大学创新药物研究中心创新药物研究与生物信息研究组;新加坡国立大学药学系计算科学与工程中心生物信息与药物设计研究组 清华大学深圳研究生院广东省化学生物学重点实验室
国际会议
南京
英文
94-115
2012-05-13（万方平台首次上网日期，不代表论文的发表时间）