title: Developing natural product drugs: Supply problems and how they have been overcome.
abstract: The development of natural product-derived drugs has some unique problems associated with the process, which can be best described as the "problem of supply". In this short review, four examples are given demonstrating how the "supply problem" was overcome using as examples the development of Picato® from a plant, Kyprolis® modified from a microbial metabolite, Halaven® a totally synthetic compound based on a marine sponge metabolite and Yondelis® isolated from a marine tunicate and now known to be from an as yet uncultured microbe in the tunicate. The methods used are described in each case and show how all scientific disciplines are necessary to succeed. All of these are antitumor agents and the time involved ranged from a low of 13years to greater than 29years from the initial identification of an active compound.
authors.affiliation: Newman Consulting LLC, 664 Crestwood Road, Wayne, PA, 19087, USA. Electronic address: djnewman664@verizon.net.
authors.forename: David J
authors.initials: DJ
authors.lastname: Newman
mesh_terms: D039903:Actinobacteria / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000600:supply & distribution*; D001688:Biological Products / Q000600:supply & distribution*; D004149:Dioxoles / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D004224:Diterpenes / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D004988:Ethers, Cyclic / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D005663:Furans / Q000138:chemical synthesis / Q000600:supply & distribution; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000600:supply & distribution; D018942:Macrolides / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D011161:Porifera / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000378:metabolism / Q000600:supply & distribution; D000077606:Trabectedin; D014561:Urochordata / Q000378:metabolism; D000095662:Polyether Polyketides
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D004149:Dioxoles; D004224:Diterpenes; D004988:Ethers, Cyclic; D005663:Furans; D007659:Ketones; D018942:Macrolides; D009842:Oligopeptides; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin; C486592:3-ingenyl angelate; C070519:halichondrin B; D000095662:Polyether Polyketides; C524865:carfilzomib; C490954:eribulin; C078846:epoxomicin
keywords: Complex syntheses; Development; Natural product drugs; Supply problems