Singh Surbhi, Nigam Vaibhav, Kasana Shivani, Kurmi Balak Das, Gupta Ghanshyam Das, Patel Preeti
Department of Pharmaceutical Chemistry and Analysis, ISF College of Pharmacy, Moga-142001, Punjab, India.
Department of Pharmaceutics, ISF College of Pharmacy, Moga-142001, Punjab, India.
Curr Top Med Chem. 2025;25(4):409-433. doi: 10.2174/0115680266331025241015084546.
The c-Met receptor, a pivotal player in oncogenesis and tumor progression, has become a compelling target for anticancer drug development. This review explores the intricate landscape of Structure-Activity Relationship (SAR) studies and molecular binding analyses performed on c-Met inhibitors. Through a comprehensive examination of various chemical scaffolds and modifications, SAR investigations have elucidated critical molecular features essential for the potent inhibition of c-Met activity. Additionally, molecular docking studies have provided invaluable insights into how c-Met inhibitors interact with their target receptor, facilitating the rational design of novel compounds with enhanced efficacy and selectivity. This review highlights key findings from recent SAR and docking studies, particularly focusing on the structural determinants that govern inhibition potency and selectivity. Furthermore, the integration of computational methodologies with experimental approaches has accelerated the discovery and optimization of c-Met inhibitors, fostering the advancement of promising candidates for clinical applications. Overall, this review underscores the pivotal role of SAR and molecular docking studies in advancing our understanding of c-Met inhibition and guiding the rational design of next-generation anticancer agents targeting this pathway.
c-Met受体是肿瘤发生和肿瘤进展中的关键角色,已成为抗癌药物研发的一个极具吸引力的靶点。本综述探讨了对c-Met抑制剂进行的构效关系(SAR)研究和分子结合分析的复杂情况。通过对各种化学骨架和修饰的全面考察,SAR研究阐明了有效抑制c-Met活性所必需的关键分子特征。此外,分子对接研究为c-Met抑制剂与其靶受体的相互作用提供了宝贵的见解,有助于合理设计具有更高疗效和选择性的新型化合物。本综述突出了近期SAR和对接研究的关键发现,特别关注决定抑制效力和选择性的结构决定因素。此外,计算方法与实验方法的结合加速了c-Met抑制剂的发现和优化,推动了有前景的临床应用候选药物的进展。总体而言,本综述强调了SAR和分子对接研究在增进我们对c-Met抑制的理解以及指导针对该途径的下一代抗癌药物的合理设计方面的关键作用。