Jangra Neha, Sharma Bharti, Kumar Deepak, Kapoor Archana
Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology Hisar-125001 India
RSC Med Chem. 2025 Jul 7. doi: 10.1039/d4md00799a.
The epidermal growth factor receptor (EGFR) family comprises four distinct members with similar framework characteristics: EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). EGFR plays a pivotal role in cellular signaling pathways that regulate key pathological processes, including apoptosis, uncontrolled cell proliferation, metastasis, and angiogenesis. However, clinically used EGFRs such as apatinib, selumetinib, gefitinib, vandetanib, and erlotinib are not selective, thereby resulting in troublesome side effects. Drug obstruction, alteration, and specificity represent a few of the primary obstacles in the development of unique key compounds as EGFR inhibitors, stimulating medicinal chemists to discover innovative chemotypes. The development of drugs that block specific stages of cancerous cells, such as EGFR, is one of the main goals of many cancer treatments, including breast and lung tumors. Thus, the current study endeavored to summarize the numerous recent advancements (2016-2024) in the research and development of diverse epidermal growth factor receptor (EGFR) inhibitors, focusing on pyrrole, indole, pyrimidine, oxadiazole, isoxazole, and other structural classes. Preclinical, clinical, structure-activity relationships (SAR) with mechanism-based and research, and other relevant data are compiled to offer directions for the scientific discovery of novel EGFR inhibitors with conceivable uses in therapy. The research trajectory of this entire field will provide incessant opportunities for the discovery of novel drug molecules with improved efficacy and selectivity.
表皮生长因子受体（EGFR）家族由四个具有相似结构特征的不同成员组成：EGFR（HER1/ErbB1）、ErbB2（HER2/neu）、ErbB3（HER3）和ErbB4（HER4）。EGFR在调节关键病理过程的细胞信号通路中起关键作用，这些病理过程包括细胞凋亡、不受控制的细胞增殖、转移和血管生成。然而，临床使用的EGFR药物如阿帕替尼、司美替尼、吉非替尼、凡德他尼和厄洛替尼没有选择性，从而导致不良副作用。药物阻碍、改变和特异性是开发独特关键化合物作为EGFR抑制剂的一些主要障碍，这刺激药物化学家去发现创新的化学类型。开发阻断癌细胞特定阶段（如EGFR）的药物是许多癌症治疗（包括乳腺癌和肺癌）的主要目标之一。因此，本研究致力于总结各种表皮生长因子受体（EGFR）抑制剂研发方面的众多最新进展（2016 - 2024年），重点关注吡咯、吲哚、嘧啶、恶二唑、异恶唑和其他结构类别。收集临床前、临床、基于机制的构效关系（SAR）研究及其他相关数据，为科学发现可用于治疗的新型EGFR抑制剂提供指导。整个领域的研究轨迹将为发现具有更高疗效和选择性的新型药物分子提供持续的机会。
