The impact of natural products upon modern drug discovery

Ganesan, A ORCID: (2008) The impact of natural products upon modern drug discovery. Current Opinion in Chemical Biology, 12 (3). pp. 306-317. ISSN 1879-0402

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In the period 1970–2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the ‘Lipinski universe’ and complies with the Rule of Five. The second is a ‘parallel universe’ that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of log P and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug.

Item Type: Article
Faculty \ School: Faculty of Science > School of Pharmacy
UEA Research Groups: Faculty of Science > Research Groups > Medicinal Chemistry (former - to 2017)
Faculty of Science > Research Groups > Chemical Biology and Medicinal Chemistry (former - to 2021)
Depositing User: Users 2731 not found.
Date Deposited: 20 Oct 2011 11:43
Last Modified: 16 Jan 2023 16:31
DOI: 10.1016/j.cbpa.2008.03.016

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