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These papers, the first of which is a perspective on the second much larger paper, should also be read in conjunction with a recent paper showing the natural product compound equivalents ( invalid metabolic panacea s (IMPS)) to the pan- assay interference compound s (PAINS) that cause major problems in HTS programs.

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That Nature in one guise or another has continued to influence the design of small molecules is shown by inspection of the information given below, where with the advantage of now 34 years of data from 1981 to 2014 the system has been able to be refined.

Inspection of the data shows the continued important role for natural products in spite of the greatly reduced level of natural-products-based drug discovery programs in major pharmaceutical houses.

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Thus, the number of new active substances (NASs) from our data set, also known as new chemical entities (NCEs), which we consider to encompass all molecules, including biologics and vaccines, hit a 24-year low of 24 in 2004 (although 7, or 29%, of these were assigned to the “ND” category), leading to a rebound to 52 in 2005, with 25% being “N” or “ND” and 37% being biologics (“B”) or vaccines (“V”).

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Similarly, if one moves to the plant kingdom, there is now a significant volume of published work that indicates that a fair number of what were thought to be “plant-derived” natural products are in fact produced “in part” and in some cases, such as maytansine, totally by interactions with endophytic microbes, frequently fungi.

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