Historically, natural products have been pharma's treasure trove. According to the Natural Products Library Initiative at the Scripps Research Institute, "from 1940s to date, 131 (74.8%) out of 175 small molecule anticancer drugs are natural product-based/inspired, with 85 (48.6%) being either natural products or derived therefrom. From 1981 to date, 79 (80%) out of 99 small molecule anticancer drugs are natural product-based/inspired, with 53 (530/0) being either natural products or derived there from. “In a sense, this is not surprising. In nature, after all, creatures — and at the more basic level, structures, such as receptors and their ligands — have been co—evolving for billions of years.
|100 μL * 10 mM (in DMSO)||35058.00|
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Despite that sort of a track record, pharma industry was turning away from natural products with the rise of combinatorial chemistry. The most probable reasons for this were:
Nevertheless. natural products as well as their derivatives continue to play a significant role in the discovery of new approved therapies, as they have done since the earliest days of medicinal research. Thus, Butler highlights that 21 natural-product-derived drugs were approved for use in Western markets during the period 1998-2004 A more recent update to this indicates an additional 19 natural-product-derived approvals during the period January 2005 to April 2010 Natural products have proven successful modulators of difficult targets such as a range of antibacterial targets and, especially, protein—protein interactions Furthermore, many researchers consider natural products and their derivatives as a privileged tools for the study and manipulation of protein function In general, renaissance of the pharma industry interest toward natural products research is observed nowadays since they provide a unique biologically relevant chemical space, especially for difficult, traditionally intractable but nevertheless high value targets. Many methodologies and approaches have been developed to eliminate the above-mentioned obstacles to research and, accordingly, to a wider application of natural substances in drug discovery. Synthesis of natural-product-derived compounds is one of them. In this case, libraries are generated around a scaffold that is identical to that of the leading natural product and which is obtained by means of chemical modification or degradation- The library members are then synthesized (preferably in combinatorial synthesis mode) from the scaffold using a step-by-step derivatization. The substitution pattern, stereochemistry, and structure of the scaffold may be set as in the natural product itself. This promising approach has been already applied at TargetMol to synthesize small cytosine-based library Furthermore, it has been successfully used to build up more than 4000 members library based on some readily available natural