南方科技大学医学院徐俊副教授团队在《Nature》发表研究论文，首次证实小分子化合物可通过充当"分子胶水"的方式稳定A类G蛋白偶联受体的二聚体1。该研究以偏向性变构调节剂AP-7-168为研究对象，揭示了这类化合物如何稳定β₂肾上腺素受体同源二聚体，阐明了A类GPCR通过二聚化实现信号偏向调控的分子机制1。
这一发现具有重要的临床应用前景1。研究表明，该成果有望解决目前临床平喘药物存在的脱敏问题，为哮喘、慢性阻塞性肺疾病等气道疾病的新药研发提供重要理论基础1。此外，相关机制不仅适用于β₂肾上腺素受体，还可推广至其他A类GPCR靶点，在神经、心血管、代谢等多个领域推动靶向创新药物的开发1。
Researchers at the Southern University of Science and Technology have made a significant breakthrough in understanding how to develop new asthma medications. Associate Professor Xu Jun's team at the university's School of Medicine published a paper titled "A biased allosteric modulator is a molecular glue for β2AR dimerization" in Nature, revealing how a biased allosteric modulator called AP-7-168 functions as a molecular glue to stabilize β2-adrenergic receptor homodimers.1 This discovery marks the first time scientists have demonstrated that a small-molecule compound can stabilize Class A G protein-coupled receptor dimers through this mechanism.1
The research elucidates the molecular mechanism by which Class A GPCRs achieve biased signal regulation through dimerization.1 By clarifying how AP-7-168 enables receptor dimerization, the team has identified a potential solution to a long-standing clinical problem: the desensitization of bronchodilator medications commonly used in asthma treatment.1 The findings provide a crucial foundation for developing new therapeutic approaches to airway diseases including asthma and chronic obstructive pulmonary disease.1 Beyond respiratory applications, the discovery's implications extend to other Class A GPCRs, potentially advancing targeted drug innovation across neurology, cardiovascular medicine, and metabolic disease research.1
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