Finding Promiscuous Old Drugs for New Uses
From research published in the last six years we have identified 34 studies that have screened libraries of FDA-approved drugs against various whole cell or target assays. These studies have each identified one or more compounds with a suggested new bioactivity that had not been described previously. We now show that 13 of these drugs were active against more than one additional disease, thereby suggesting a degree of promiscuity. We also show that following compilation of all the studies, 109 molecules were identified by screening in vitro. These molecules appear to be statistically more hydrophobic with a higher molecular weight and AlogP than orphan-designated products with at least one marketing approval for a common disease indication or one marketing approval for a rare disease from the FDA’s rare disease research database. Capturing these in vitro data on old drugs for new uses will be important for potential reuse and analysis by others to repurpose or reposition these or other existing drugs. We have created databases which can be searched by the public and envisage that these can be updated as more studies are published.
KEY WORDScheminformatics HTS old drugs repositioning repurposing
ACKNOWLEDGMENTS and DISCLOSURES
SE gratefully acknowledges David Sullivan (Johns Hopkins University) for discussing and suggesting references for JHCCL. Accelrys are kindly thanked for providing Discovery Studio.
SE consults for Collaborative Drug Discovery, Inc. on a Bill and Melinda Gates Foundation: Grant#49852 “Collaborative drug discovery for TB through a novel database of SAR data optimized to promote data archiving and sharing.”
- 5.Shim JS, Matsui Y, Bhat S, Nacev BA, Xu J, Bhang HE, et al. Effect of nitroxoline on angiogenesis and growth of human bladder cancer. J Natl Cancer Inst. 2010;102(24):1855–73Google Scholar
- 29.Ekins S, Hohman M, Bunin BA. Pioneering use of the cloud for development of the collaborative drug discovery (cdd) database. In: Ekins S, Hupcey MAZ, Williams AJ, editors. Collaborative computational technologies for biomedical research, vol. Hoboken: Wiley; 2010. in press.Google Scholar
- 36.Ekins S, Williams AJ, Krasowski MD, Freundlich JS. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discov Today 2011;16(7–8):298–310.Google Scholar
- 41.Williams AJ. Reviewing data quality in the NCGC pharmaceutical collection browser. http://www.chemconnector.com/2011/04/28/reviewing-data-quality-in-the-ncgc-pharmaceutical-collection-browser/.