title: Rational approaches to natural-product-based drug design.
abstract: Natural-product-based drug discovery has encountered significant challenges during the past decade. In recent years the pharmaceutical industry has placed low emphasis on natural-product-based drug discovery efforts because of an increasing reliance on newer technologies, such as combinatorial synthesis and high-throughput screening, and their associated approaches to drug discovery. However, recent natural-product-based lead-identifying strategies have successfully and rapidly integrated rational approaches that exploit and evolve the structural diversity provided by nature. These rational approaches include the application of structure- and ligand-based design, relationship building between biosynthetic enzymes and targets as well as within the target and natural product scaffold space, and biology-oriented synthesis-guided library design. This review focuses on the recent clinical and preclinical development of natural-product-based compounds derived from these rational approaches, and is organized according to disease areas as well as novel concepts that may provide a rational basis for future developments.
authors.affiliation: AnalytiCon Discovery GmbH, Hermannswerder Haus 17, D-14473 Potsdam, Germany.
authors.forename: Lars Ole
authors.initials: LO
authors.lastname: Haustedt
authors.forename: Christian
authors.initials: C
authors.lastname: Mang
authors.forename: Karsten
authors.initials: K
authors.lastname: Siems
authors.forename: Hajo
authors.initials: H
authors.lastname: Schiewe
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001688:Biological Products / Q000737:chemistry* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products