(1351) Fda-approved Drugs Derived from Natural Products

Objectives:

Objective: This project endeavors to present a comprehensive overview of FDA-approved drugs derived from natural products, with a focus on understanding their utilization as pharmaceuticals and identifying key characteristics that render natural products suitable for drug development.

Methods:

Methods: A systematic approach was used to generate a list of FDA-approved natural product drugs from the scientific literature and FDA databases. Exclusion criteria were established, eliminating macromolecules, essential human micronutrients, human biomolecules, and drugs with non-natural, synthetic modifications. Extensive literature searches were conducted on the eligible drugs to trace their source organisms, initial years of FDA approval or market entry, available dosage forms, administration routes, approved indications, chemical classes, marketing statuses, mechanisms of action, and occurrence on a list of top 200 pharmaceuticals by prescription. An equivalent number of non-natural drugs was randomly selected as a comparison sample.

Results:

Results: A total of 93 medications were identified as unmodified, natural, small-molecule drugs. More than half of these belonged to either the alkaloid/pseudoalkaloid or polyketide/macrolide chemical classes. Nearly 90% were sourced from bacteria or plants. Antibacterials were the most common drug category and inhibition of protein synthesis the most common mechanism of action. Compared to a random sample of non-natural drugs, the natural drugs were less likely to be among the top 200 most prescribed medicines (11% vs. 2%) and were more likely to be administered by non-oral routes (23% and 10% vs. 43% and 21% for injection and topical routes, respectively), but were no more likely to have a discontinued marketing status (18% vs. 22%). Notably, FDA approval or market entry of natural drugs peaked prior to 1942 and steadily declined in the ensuing decades, while non-natural drugs demonstrated an inverse trend.

Conclusions:

Conclusion: This study provided a survey of unmodified, natural small molecules that have been approved as drugs by the FDA and identified many of their key attributes, including the most common structural classes, natural sources, mechanisms of action, therapeutic categories, and routes of delivery. These results cast light on the roles natural drugs have historically played in pharmacotherapy and provide insight into what niches they might be best poised to fill in the future