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Paclitaxel (Taxol®): A success story with valuable lessons for natural product drug discovery and development
Author(s) -
Cragg Gordon M.
Publication year - 1998
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/(sici)1098-1128(199809)18:5<315::aid-med3>3.0.co;2-w
Subject(s) - paclitaxel , drug discovery , natural product , drug development , bryostatin 1 , drug , computer science , computational biology , risk analysis (engineering) , medicine , biology , cancer , pharmacology , bioinformatics , genetics , gene , biochemistry , activator (genetics)
The discovery and development of paclitaxel, which covered a time span of some 30 years, has provided some important lessons for those involved in natural product drug discovery and development. These include the adoption of novel screens as they become available, the elucidation of mechanisms of action, and addressing the supply issue at an early stage of development. These issues, as applied to paclitaxel, are illustrated. The development of the NCI human cancer cell line screen, and its application to mechanistic studies through use of COMPARE analyses, are discussed, as is the production of the marine‐derived anticancer agent, bryostatin 1, which provides another illustration of a successful approach to solving a supply issue. The history of the development of paclitaxel also illustrates the importance of multidisciplinary collaboration, and the various mechanisms used by the NCI Developmental Therapeutics Program for promoting such collaboration are presented. © 1998 John Wiley & Sons, Inc. Med Res Rev, 18, No. 5, 315–331, 1998.