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用小分子抑制剂向PD-1/PD-L1相互作用的癌症免疫疗法的进展

Feng Zhang¹, Sivaramakarthikeyan Ramar², Yu Wang¹

¹Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Deqing 313299, China; Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Deqing 313299, China.

Bioorganic & medicinal chemistry

|May 14, 2025

概括

针对PD-1/PD-L1通路的小分子抑制剂为癌症治疗提供了抗体的经济有效替代品. 本综述详细介绍了它们的设计,机制以及克服当前治疗局限性的潜力.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
药用化学医学化学

背景情况:

癌症的免疫规避涉及PD-1/PD-L1通路.
针对PD-1/PD-L1的单克隆抗体在临床上取得了成功,但面临着成本和瘤透等挑战.
小分子抑制剂是一个有前途的替代品,具有改进的特性.

研究的目的:

审查PD-1/PD-L1通路的小分子抑制剂的进展.
分析它们的机制,结构设计和癌症治疗中的治疗潜力.
为这些抑制剂的设计逻辑和未来方向提供见解.

主要方法:

小分子PD-1/PD-L1抑制剂的各种分子结构的系统分类.
分析相关的工业案例和最近的研究成果.
药物化学原理与临床需求的整合.

主要成果:

关键的创新包括双支架和异环框架,提高结合效率和免疫激活.
与抗体相比,小分子提供了改善的瘤透和成本效益.
审查系统地对结构进行分类,并讨论设计策略.

结论:

小分子PD-1/PD-L1抑制剂代表了癌症免疫治疗的重大进展.
它们的设计和开发提供了一个可行的策略,以克服当前基于抗体的治疗方法的局限性.
在这个领域的持续创新有望为更有效和更容易获得的癌症治疗提供希望.

关键词:

癌症免疫疗法癌症免疫疗法药物设计药物设计免疫检查点抑制剂免疫检查点抑制剂在PD-1/PD-L1路径上.小分子抑制剂小分子抑制剂

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