Drug repositioning (also known as drug repurposing, re-profiling, re-tasking or therapeutic switching) is the application of known drugs and compounds to treat new indications (i.e., new diseases).
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A significant advantage of drug repositioning over traditional drug development is that since the repositioned drug has already passed a significant number of toxicity and other tests, its safety is known and the risk of failure for reasons of adverse toxicology are reduced. More than 90% of drugs fail during development, and this is the most significant reason for the high costs of pharmaceutical R&D. In addition, repurposed drugs can bypass much of the early cost and time needed to bring a drug to market. It significantly reduces the transition of bench research work to treatment at bedside. On the other hand, drug repositioning faces some challenges itself since the intellectual property issues surrounding the original drug may be complex and from a commercial point of view it may not always make sense to take such a drug to market.
Drug repositioning has been growing in importance in the last few years as an increasing number of drug development and pharmaceutical companies see their drug pipelines drying up and realize that many previously promising technologies have failed to deliver ‘as advertised’. Computational approaches based on virtual screening of comprehensive libraries of approved and other human use compounds against large numbers of protein targets simultaneously have been developed to enhance the efficiency and success rates of drug repositioning, particularly in terms of high-throughput shotgun repurposing.
Commercialization
Smaller companies, including Ore Pharmaceuticals, Biovista, GVK BIO, Numedicus, Melior Discovery and SOM Biotech are also performing drug repositioning on a systematic basis. These companies use a combination of approaches including in silico biology and in vivo/in vitro experimentation to assess a compound and develop and confirm hypotheses concerning its usage for new indications.
Examples
Using drug repositioning, pharmaceutical companies have achieved a number successes, for example Pfizer's Viagra in erectile dysfunction and Celgene's thalidomide in severe erythema nodosum leprosum.
One notable example of drug repurposing is taking the partial mu-opioid receptor agonist buprenorphine - which has been prescribed for control of moderate pain for decades in low dosages in the form of Temgesic 200mcg sublingual tablets, Buprenex 300mcg/mL ampoules - and marketing a high-dosage formulation (Subutex 2 mg and 8 mg) for the interruption and maintenance of heroin and other opioid addictions, which it has proven very beneficial for, with over 200,000 people in the United States alone on buprenorphine maintenance. Some of the reasons for this are that the drug has a ceiling effect - higher doses do not cause further activation of opioid receptors - and a very long half-life in >2 mg dosages. It also has an extremely high binding affinity for opioid receptors, which keeps the drug from being displaced by opioids like Dilaudid, heroin, morphine, and oxycodone, with the result that a user maintained on it can not get high no matter what dosage taken of most opioids. The only opioids that may be able to break through the buprenorphine blockade (which are required in an acute care setting if a buprenorphine patient requires pain relief, as no standard opioids are strong enough) - drugs with similar or higher binding affinities to buprenorphine itself - are the fentanil-class opioids, and the Bentley-series opioids (cf. etorphine, dihydroetorphine), which are rarely primary drugs of abuse and not often found on the streets. Buprenorphine itself is a modified Bentley-series opioid.
Requip is another notable example of drug repurposing. Originally developed as an anti-Parkinsonian agent, it has found application in the treatment of both Restless Legs Syndrome and SSRI-induced sexual dysfunction.
Colesevelam is another example of drug repurposing. Originally developed as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia as monotherapy, it has also gained approval to improve glycemic control in adults with type 2 diabetes mellitus.
Another example of drug repurposing is that of gabapentin, and its chemical cousin pregabalin. Originally developed as anti-epileptics, they have found more use treating anxiety disorders and neuropathic pain than as seizure medications.
Plerixafor, initially developed as an HIV drug to block viral entry in the cell via the chemokine co-receptor CXCR4, failed in its initial medical indication. Nevertheless, it was noticed that the drug induced peripheral blood leukocytosis within which peripheral blood CD34 hematopoietic stem cells were found. On basis of this observation, the drug has been re-purposed as a stem cell mobilizing drug.