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The re-emergence of natural products for drug discovery in the genomics era

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TLDR
This work reviews strategies for natural product screening that harness the recent technical advances that have reduced technical barriers and assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products.
Abstract
Natural products have been a rich source of compounds for drug discovery. However, their use has diminished in the past two decades, in part because of technical barriers to screening natural products in high-throughput assays against molecular targets. Here, we review strategies for natural product screening that harness the recent technical advances that have reduced these barriers. We also assess the use of genomic and metabolomic approaches to augment traditional methods of studying natural products, and highlight recent examples of natural products in antimicrobial drug discovery and as inhibitors of protein-protein interactions. The growing appreciation of functional assays and phenotypic screens may further contribute to a revival of interest in natural products for drug discovery.

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Natural Products as Sources of New Drugs from 1981 to 2014

TL;DR: This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012, and the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide.
Journal ArticleDOI

Natural products in drug discovery: advances and opportunities.

TL;DR: In this article, the authors summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities, and discuss the potential of using natural products as drug leads.
Journal ArticleDOI

Counting on natural products for drug design

TL;DR: This work highlights the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempts to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.
Journal ArticleDOI

Organic synthesis provides opportunities to transform drug discovery

TL;DR: This Perspective highlights some of the most pressing challenges to be overcome from the industrial viewpoint — such as the development of reactions tolerating specific functionalities — and encourages stronger industry–academia relationships.
References
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Journal ArticleDOI

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
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Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection.

TL;DR: These mutants—the ‘Keio collection’—provide a new resource not only for systematic analyses of unknown gene functions and gene regulatory networks but also for genome‐wide testing of mutational effects in a common strain background, E. coli K‐12 BW25113.
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Natural Products as Sources of New Drugs over the Last 25 Years

TL;DR: This review is an updated and expanded version of two prior reviews that were published in this journal in 1997 and 2003 and is able to identify only one de novo combinatorial compound approved as a drug in this 25 plus year time frame.
Journal ArticleDOI

In vivo activation of the p53 pathway by small-molecule antagonists of MDM2.

TL;DR: In this article, the authors identify potent and selective small-molecule antagonists of MDM2 and confirm their mode of action through the crystal structures of complexes, leading to cell cycle arrest, apoptosis, and growth inhibition of human tumor xenografts.
Journal ArticleDOI

Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010

TL;DR: This review is an updated and expanded version of the three prior reviews and adds a new designation, "natural product botanical" or "NB", to cover those botanical "defined mixtures" that have now been recognized as drug entities by the FDA and similar organizations.
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