Chen Roufen, Yuan Dandan, Ma JunJie
School of Medicine, Huaqiao University, Quanzhou, 362000, China.
Future Med Chem. 2022 Jan;14(2):97-113. doi: 10.4155/fmc-2021-0256. Epub 2021 Dec 6.
Immunotherapy inhibiting the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) interaction has emerged as one of the most attractive cancer treatment strategies. So far, the clinically used PD-1/PD-L1 inhibitors are monoclonal antibodies, but monoclonal antibodies have several limitations, such as poor pharmacokinetic properties, unchecked immune responses and high production cost. The development of small-molecule inhibitors targeting PD-1/PD-L1 interaction is showing great promise as a potential alternative or complementary therapeutic approach of monoclonal antibodies. In this article, the authors classify the reported biphenyl small-molecule inhibitors into symmetrical and asymmetrical types based on their structural features and further review their representative inhibitors and biological activities, as well as the binding models for providing insight into further exploration of more potent biphenyl small-molecule inhibitors targeting PD-1/PD-L1 interaction.
抑制程序性死亡蛋白1/程序性死亡配体1（PD-1/PD-L1）相互作用的免疫疗法已成为最具吸引力的癌症治疗策略之一。到目前为止，临床上使用的PD-1/PD-L1抑制剂是单克隆抗体，但单克隆抗体存在一些局限性，如药代动力学性质不佳、免疫反应不受控制以及生产成本高昂。开发靶向PD-1/PD-L1相互作用的小分子抑制剂作为单克隆抗体的潜在替代或补充治疗方法显示出巨大潜力。在本文中，作者根据其结构特征将已报道的联苯小分子抑制剂分为对称型和不对称型，并进一步综述了它们的代表性抑制剂、生物学活性以及结合模型，以便为进一步探索更有效的靶向PD-1/PD-L1相互作用的联苯小分子抑制剂提供思路。
