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Selection criteria. The NCC consists almost entirely of drugs that have been in phase I-III clinical trials and have not been represented in other arrayed collections. These compounds also have favorable attributes for inclusion in a screening collection, such as purity, solubility and commercial availability for re-supply.
Drug-likeness. By definition, compounds that have been tested in human clinical trials have highly developed properties of drug-likeness, such as bioavailability and stability. Having been used in humans, most of these compounds also have well-characterized safety profiles.
Extensive Bioactivity Profiles. The NCC compounds are part of the screening library for the NIH Roadmap Molecular Libraries Screening Centers Network (MLSCN). Thus, extensive bioactivity data on these compounds from dozens of high throughput screens will be publicly available through PubChem. Through ongoing screening within and outside the MLSCN, the body of knowledge about these compounds will be continually expanding.
Format. The collection contains approximately 450 compounds arrayed in six 96-well plates. 50 μl of each compound is supplied, as an approximately 10 mM solution in 100% DMSO. Please note that compounds were plated at varying concentrations due to solubility levels.
Resupply. All of the compounds in the NCC are commercially available for re-supply. Sources of compounds for the NCC are listed in the compound database.
The following articles describe discoveries of novel uses for existing drugs:
1. Abbott, A (2002) Neurologists strike gold in drug screen effort, Nature 417:109. http://www.nature.com/nature/journal/v417/n6885/full/417109a.html
2. Corcoran, LJ, Mitchison TJ, Liu Q. (2004) A novel action of histone deacetylase inhibitors in a protein aggresome disease model. Curr Biol 14: 488-92.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15043813
3. Stravrovskaya IG, et al. (2004) Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology. J Exp med 200: 211-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15263028
4. Lunn MR, et al. (2004) Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. Chem Biol 11: 1489-93.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15555999
5. Rothstein JD, et al. (2005). Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433: 73-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15635412
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