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Back in 1997, a suggestion to apply the concept of synthetic lethality towards the development of selective, less toxic, cancer drugs and anticancer targets, was brought forward. The availability of large scale synthetic, low-molecular-weight chemical libraries seemed to lend itself to the concept. Human/mouse genome-wide siRNAs and shRNA-expressing libraries allowing high throughput screening for target genes synergistic lethal with defined human cancer aberrations, also raised high hopes of a soon to be established selective therapy. Sixteen years later, the major experimental aspects relating to the implementation of this more focused approach to cancer drug discovery, is briefly and critically reviewed.
Pubmed ID: 23962561
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Portal for preclinical information and research materials, including web-accessible data and tools, NCI-60 Tumor Cell Line Screen, compounds in vials and plates, tumor cells, animals, and bulk drugs for investigational new drug (IND)-directed studies. DTP has been involved in the discovery or development of more than 70 percent of the anticancer therapeutics on the market today, and will continue helping the academic and private sectors to overcome various therapeutic development barriers, particularly through supporting high-risk projects and therapeutic development for rare cancers. Initially DTP made its drug discovery and development services and the results from the human tumor cell line assay publicly accessible to researchers worldwide. At first, the site offered in vitro human cell line data for a few thousand compounds and in vitro anti-HIV screening data for roughly 42,000 compounds. Today, visitors can find: * Downloadable in vitro human tumor cell line data for some 43,500 compounds and 15,000 natural product extracts * Results for 60,000 compounds evaluated in the yeast assay * In vivo animal model results for 30,000 compounds * 2-D and 3-D chemical structures for more than 200,000 compounds * Molecular target data, including characterizations for at least 1,200 targets, plus data from multiple cDNA microarray projects In addition to browsing DTP's databases and downloading data, researchers can request individual samples or sets of compounds on 96-well plates for research, or they can submit their own compounds for consideration for screening via DTP's online submission form. Once a compound is submitted for screening, researchers can follow its progress and retrieve data using a secure web interface. The NCI has collected information on almost half a million chemical structures in the past 50 years. DTP has made this information accessible and useful for investigators through its 3-D database, a collection of three-dimensional structures for more than 200,000 drugs. Investigators use the 3-D database to screen compounds for anticancer therapeutic activity. Also available on DTP's website are 127,000 connection tables for anticancer agents. A connection table is a convenient way of depicting molecular structures without relying on drawn chemical structures. As unique lists of atoms and their connections, the connection tables can be indexed and stored in computer databases where they can be used for patent searches, toxicology studies, and precursor searching, for example.
View all literature mentionsCurated protein-protein and genetic interaction repository of raw protein and genetic interactions from major model organism species, with data compiled through comprehensive curation efforts.
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