An ‘orphan’ receptor with implications in blood glucose regulation and cell death is shown to be responsive to a small molecule in a study online this week in Nature Chemical Biology. The discovery reveals a compound that can be used to investigate receptor function and may also serve as inspiration for drug development efforts.
Nur77 is a receptor which has a site to bind a small molecule but no such molecules have been identified, making the protein an ‘orphan’. However, the protein is active despite this, leading to the conclusion that the protein would not be affected by a small molecule partner at all. Thus, it came as a surprise when Qiao Wu and colleagues identified a compound, cytosporone B, that binds to Nur77 and promotes its normal activity in isolated cells and in mice.
Nur77 affects the expression of many genes, including some that affect blood glucose levels and others that cause cell death. The binding of cytosporone B to Nur77 increased blood glucose levels and, after longer periods, caused apoptosis, a form of cell death. This new compound will therefore be helpful in understanding these complicated cellular processes and may serve as inspiration for drug development efforts.
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