title: The value of nature's natural product library for the discovery of New Chemical Entities: the discovery of ingenol mebutate.
abstract: In recent decades, 'Big Pharma' has invested billions of dollars into ingenious and innovative strategies designed to develop drugs using high throughput screening of small molecule libraries generated on the laboratory bench. Within the same time frame, screening of natural products by pharmaceutical companies has suffered an equally significant reduction. This is despite the fact that the complexity, functional diversity and druggability of nature's natural product library are considered by many to be superior to any library any team of scientists can prepare. It is therefore no coincidence that the number of New Chemical Entities reaching the market has also suffered a substantial decrease, leading to a productivity crisis within the pharmaceutical sector. In fact, the current dearth of New Chemical Entities reaching the market in recent decades might be a direct consequence of the strategic decision to move away from screening of natural products. Nearly 700 novel drugs derived from natural product New Chemical Entities were approved between 1981 and 2010; more than 60% of all approved drugs over the same time. In this review, we use the example of ingenol mebutate, a natural product identified from Euphorbia peplus and later approved as a therapy for actinic keratosis, as why nature's natural product library remains the most valuable library for discovery of New Chemical Entities and of novel drug candidates.
authors.affiliation: GeneCology Research Centre, Faculty of Science, Health, Engineering and Education, University of the Sunshine Coast, Maroochydore DC, QLD 4558, Australia. Electronic address: sogbourn@usc.edu.au.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Ogbourne
authors.affiliation: QIMR Berghofer Medical Research Institute, Locked Bag 2000, Post Office Royal Brisbane Hospital, QLD 4029, Australia. Electronic address: Peter.Parsons@qimrberghofer.edu.au.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Parsons
mesh_terms: D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D055808:Drug Discovery; D028481:Euphorbia / Q000737:chemistry; D006801:Humans; D055623:Keratosis, Actinic / Q000188:drug therapy*; D008519:Medicine, Traditional
chemical_list: C486592:3-ingenyl angelate; D001688:Biological Products; D004224:Diterpenes
keywords: Cancer; Drug discovery; Euphorbia peplus; Ingenol mebutate; Natural product; PEP005