Natural Drugs: Trends, Properties, and Decline in FDA Approvals.

The purpose of this review is to better characterize the contribution and properties of FDA-approved drugs that can be found unmodified in nature. Defined inclusion criteria were applied to drugs identified in previous studies and in annual FDA approval reports to compile a comprehensive list of approved drugs found in nature. Databases and scientific literature were searched to identify chemical and drug properties of these entities, including chemical classes, approval years, drug indications, and approved delivery methods. A random sample of FDA-approved drugs not found in nature was also created for comparison. Drugs from nature are estimated to represent 5% of FDAapproved drugs. The most common classes of natural product drugs are alkaloids, oligopeptides, polyphenols, and polyketides. Approvals of unmodified drugs from nature have declined at a rate of about two per decade since the mid-1900s. Compared to non-natural drugs, drugs from nature are more likely to be used as antibacterials and for dermatological conditions. Natural drugs are also less likely to be delivered orally and more likely to have narrow therapeutic indexes. Given the limitations of unmodified natural products as drugs, the pharmaceutical sciences will likely continue to play an important role in improving the drug-likeness of natural scaffolds.