Drug Repositioning – Learn more with AuroBlog

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Drug Repositioning Aspirin

Drug: Aspirin, introduced as an analgesic but the number of off-label uses of medicines is growing at an impressive rate.

Original Indication: Inflammation, Pain

New Indication: Antiplatelet

In 1988, the aspirin component of the Physicians’ Health Study, a randomized, double-blind, placebo-controlled trial of 22,000 apparently healthy men, was terminated early because of the extreme reduction in the risk of a first myocardial infarction. Hence in 1988, aspirin’s role expanded beyond that of pain reliever to that of potential lifesaver when the US Food and Drug Administration (FDA) proposed using aspirin to reduce the risk of recurrent myocardial infarction and to prevent recurrent transient ischemic attacks or ministrokes in men. Recently, Bayer Health Care filed a citizen petition with the FDA to broaden the professional labeling of aspirin to include indications for the prevention of a first myocardial infarction in individuals at moderate or greater risk of coronary heart disease.

Mechanism of action: Aspirin inhibits platelet cyclooxygenase, a key enzyme in thromboxane A2 (TXA2) generation. Thromboxane A2 triggers reactions that lead to platelet activation and aggregation, aspirin acts as a potent antiplatelet agent by inhibiting generation of this mediator. These effects last for the life of the anucleate platelet, approximately 7 to 10 days.

Drug Repositioning Nitroxoline

Drug: Nitroxoline, an old antibiotic used for the treatment of urinary tract infections (UTI).

New Indication: Anticancer Drug. Shim et al. first reported anticancer activity of nitroxoline in 2010.

Mechanism of action:

* Inhibiting human MetAP2 and sirtuins in endothelial cells
* Inducing premature senescence and inhibiting angiogenesis
* Inhibiting cathepsin B

Given that nitroxoline has a long retention time in urine, it was postulated that the drug might be particularly effective in urological cancers such as bladder cancer. Since it is inhibiting cathepsin B, it might have a role in suppressing breast cancer cell invasion. Currently the drug development is in Preclinical trials.

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