Abstract：
The ligand-sensing transcription factor retinoid X receptor (RXR) is the universal heterodimer partner of nuclear receptors and involved in multiple physiological processes. Its pharmacological modulation holds therapeutic potential in cancer and neurodegeneration but many available RXR ligands lack specificity. The sesquiterpenoid valerenic acid has been identified as RXR agonist with unprecedented subtype and homodimer preference. Here, we identified simplified mimetics of the complex natural product by rational design and virtual screening that exhibited similar activity profiles on RXR and informed about structural elements contributing to the favorable activity.
摘要：
配体敏感转录因子类视黄醇X受体（RXR）是核受体的通用异二聚体伴侣，参与多个生理过程。其药理学调节在癌症和神经变性中具有治疗潜力,但许多可用的RXR配体缺乏特异性。倍半萜戊酸已被鉴定为具有前所未有的亚型和同源二聚体偏好的RXR激动剂。这里,我们通过合理设计和虚拟筛选确定了复杂天然产物的简化模拟物,这些模拟物在RXR上表现出相似的活性谱,并了解了有助于有利活性的结构元件.
