Development of a Natural Products-Based High Throughput Screen: Identification of Correctors of Cystic Fibrosis Misfolding Mutants

Natural products or their derivatives have accounted for most of our current drugsdemonstrating their unique status asprivilegedmolecules that are well adapted for therapeutic useHowevernatural products have previously been unsuitable for modernhigh throughputHTdrug discovery screening approachesand as suchwere long ago abandoned in drug discovery programs of large pharmaThe substitute has been highthroughput screening of combinatorial chemical librariesThese unnatural chemical libraries have yielded few new pharmaceutics leading to a significant decline in pharmaceutical drug discovery productivityRecent research in the field of synthetic biology has identified numerous biosynthetic pathwayslargely from microbial sourcesthat have the capacity to produce tremendous numbers of novel natural products that are suitable for high throughput screeningIn this workSynthetic Biodesign will combine a novel biosynthetic approach with a novel whole animal high throughput screen to demonstrate that natural products can be reintegrated into the drug discovery pipeline and this can be done using modern HT methodologiesIn addition to restoring this productive class of molecules to modern day drug discoveryit is expected that badly needed new therapeutics will be identified for the treatment of Cystic Fibrosis Natural products and their derivatives have been the greatest source of our current pharmaceuticsHowevermost pharmaceutical companies have moved away from the use of natural products in their drug discovery programsto devastating effectThis was necessary due to the adoption of high throughput screening approaches for which natural products were not readily adaptableSynthetic Biodesign has developed a novel natural product based drug discovery platform that is compatible with modern high throughput screening methodsIn the proposed workSynthetic Biodesign will use this platform to provide badly needed new pharmaceutics for the treatment of important human diseasesIn particularnovel therapeutics for the treatment of Cystic fibrosis will be developed