Research press release


Nature Medicine

Combination drugs reduce side-effects


エストロゲンは、摂食行動とエネルギー消費を変化させるため、肥満や2型糖尿病の治療に利用できるとされているが、腫瘍の成長促進など、望ましくない副作用を引き起こす可能性もある。Matthias Tschopoたちは、エストロゲンをGLP-1と化学的に結合させることによって代謝にかかわる組織へと選択的に送り込み、この問題を克服した。この連結化合物は、両方の化合物を単独で投与した場合に比べ、肥満マウスの代謝に対する有益な効果が大きいことも明らかになった。


The combination of two compounds, estrogen and the gut hormone GLP-1, results in a more selective and potent metabolic drug with fewer side effects, according to research published this week in Nature Medicine.

Estrogen, by modulating feeding behavior and energy expenditure, has been suggested as a therapy for obesity and type 2 diabetes; however, it can also cause unwanted effects, such as tumor growth promotion. Matthias Tschop and colleagues circumvent this issue by chemically linking estrogen to the hormone GLP-1 to selectively target metabolically-relevant tissue. The authors note that the conjugated compound also has greater beneficial metabolic effects in obese mice compared to either native compound administered alone."

They conclude that this chemical approach may lead to other safer drug combinations, such as widely used glucocorticoids, to treat a variety of different diseases. Long-term toxicological studies are needed however, to ensure that negative effects on cell types that express receptors for both GLP-1 and estrogen, such as pancreatic beta cells, does not occur.

doi: 10.1038/nm.3009


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