G protein-coupled receptors (GPCRs) are the largest class of receptors in the human genome and some of the most common drug targets. It is now well established that GPCRs can signal through multiple transducers, including heterotrimeric G proteins, GPCR kinases and β-arrestins. While these signalling pathways can be activated or blocked by 'balanced' agonists or antagonists, they can also be selectively activated in a 'biased' response. Biased responses can be induced by biased ligands, biased receptors or system bias, any of which can result in preferential signalling through G proteins or β-arrestins. At many GPCRs, signalling events mediated by G proteins and β-arrestins have been shown to have distinct biochemical and physiological actions from one another, and an accurate evaluation of biased signalling from pharmacology through physiology is crucial for preclinical drug development. Recent structural studies have provided snapshots of GPCR–transducer complexes, which should aid in the structure-based design of novel biased therapies. Our understanding of GPCRs has evolved from that of two-state, on-and-off switches to that of multistate allosteric microprocessors, in which biased ligands transmit distinct structural information that is processed into distinct biological outputs. The development of biased ligands as therapeutics heralds an era of increased drug efficacy with reduced drug side effects.

G蛋白偶联受体（GPCR）是人类基因组中最大的受体类别，也是一些最常见的药物靶标。现已公认，GPCR可以通过多种传感器发出信号，包括异源三聚体G蛋白，GPCR激酶和β-arrestin。尽管这些信号传导途径可以被“平衡”的激动剂或拮抗剂激活或阻断，但它们也可以在“偏向”响应中被选择性激活。偏向的配体，偏向的受体或系统的偏向都可以引起偏倚的应答，这些偏见中的任何一个都可能导致通过G蛋白或β-arrestin发出优先信号。在许多GPCR中，由G蛋白和β-arrestin介导的信号转导事件已显示出彼此具有独特的生化和生理作用，从药理学到生理学的偏向信号的准确评估对于临床前药物开发至关重要。最近的结构研究提供了GPCR-转导子复合物的快照，这应有助于新的偏倚疗法的基于结构的设计。我们对GPCR的理解已从两种状态的通断开关演变为对多态变构微处理器的理解，在这种状态下，有偏向的配体会传递不同的结构信息，这些信息将被加工成不同的生物输出。偏向配体作为治疗剂的发展预示着药物功效增强，药物副作用减少的时代。这应该有助于新的偏倚疗法的基于结构的设计。我们对GPCR的理解已从两种状态的通断开关演变为对多态变构微处理器的理解，在这种状态下，有偏向的配体会传递不同的结构信息，这些信息将被加工成不同的生物输出。偏向配体作为治疗剂的发展预示着药物功效增强，药物副作用减少的时代。这应该有助于新的偏倚疗法的基于结构的设计。我们对GPCR的理解已从两种状态的通断开关演变为对多态变构微处理器的理解，在这种状态下，有偏向的配体会传递不同的结构信息，这些信息将被加工成不同的生物输出。偏向配体作为治疗剂的发展预示着药物功效增强，药物副作用减少的时代。