Repurposing approved drugs on the pathway to novel therapies复制标题

将批准的药物重新用于新疗法的途径

The time and cost of developing new drugs have led many groups to limit their search for therapeutics to compounds that have previously been approved for human use. Many "repurposed" drugs, such as derivatives of thalidomide, antibiotics, and antivirals have had clinical success in treatment areas well beyond their original approved use. These include applications in treating antibiotic-resistant organisms, viruses, cancers and to prevent burn scarring. The major theoretical justification for reusing approved drugs is that they have known modes of action and controllable side effects. Coadministering antibiotics with inhibitors of bacterial toxins or enzymes that mediate multidrug resistance can greatly enhance their activity. Drugs that control host cell pathways, including inflammation, tumor necrosis factor, interferons, and autophagy, can reduce the "cytokine storm" response to injury, control infection, and aid in cancer therapy. An active compound, even if previously approved for human use, will be a poor clinical candidate if it lacks specificity for the new target, has poor solubility or can cause serious side effects. Synergistic combinations can reduce the dosages of the individual components to lower reactivity. Preclinical analysis should take into account that severely ill patients with comorbidities will be more sensitive to side effects than healthy trial subjects.

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