Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China.
Eur J Med Chem. 2024 Nov 5;277:116786. doi: 10.1016/j.ejmech.2024.116786. Epub 2024 Aug 20.
PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development, highlighting fundamental discoveries that laid the foundation for subsequent advancements. Optimization strategies, including medicinal chemistry approaches and structural modifications, are scrutinized for their contributions to enhancing inhibitor potency, selectivity, and pharmacokinetic properties. The translation from preclinical studies to clinical trials is examined, emphasizing pivotal trials that evaluated efficacy and safety profiles. Challenges encountered during clinical development are critically assessed. Finally, the review discusses ongoing research directions and prospects for PI3K inhibitors, underscoring these agents' continuous evolution and therapeutic potential.
PI3K 抑制剂因其在各种细胞过程中的关键作用而成为有前途的治疗药物，特别是在 PI3K 途径经常失调的癌症中。本综述探讨了 PI3K 抑制剂从实验室发现到临床应用的演进历程。这段旅程始于对 PI3K 信号和抑制剂开发的早期实验室研究，强调了为后续进展奠定基础的基本发现。优化策略，包括药物化学方法和结构修饰，因其对提高抑制剂的效力、选择性和药代动力学特性的贡献而受到审查。从临床前研究到临床试验的转化得到了检验，强调了评估疗效和安全性的关键试验。临床开发中遇到的挑战得到了批判性评估。最后，该综述讨论了 PI3K 抑制剂的当前研究方向和前景，强调了这些药物的持续进化和治疗潜力。
