Abstract
Drug targets for the treatment of obesity and comorbidities represent an ever-renewable source of research opportunities worldwide. One of the earliest is the leptin–leptin receptor system that was discovered in the mid-1990s. Leptin, a satiety hormone, is overproduced in overweight patients but the protein is unable to cross the blood–brain barrier and remains inactive. Circulating high levels of leptin induces a series of conditions that would not be manifested without leptin overproduction, including various forms of cancer and inflammatory and cardiovascular diseases. Current pharmaceutical research focuses on improving the blood–brain barrier penetration of leptin receptor agonists and the development of monofunctional antagonists with broad spectrum therapeutic efficacies but without unwanted side effects. Designer peptides with their expanded chemical space as well as well controllable receptor binding and elimination properties slowly replace full-sized leptin products in the drug development pipeline.
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