Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan
{"title":"From Lab to Target: Pyrazole, Pyrazoline and Fused Pyrazole Derivatives as Receptor Tyrosine Kinase Inhibitors in Cancer Therapy","authors":"Michael M. Sawiris, Omneya M. Khalil, Peter A. Halim, Marwa S. A. Hassan","doi":"10.1002/ardp.70061","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA-approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR-2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole-based anticancer agents targeting receptor tyrosine kinases.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.70061","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Pyrazole derivatives have emerged as versatile scaffolds in the development of receptor tyrosine kinase inhibitors, offering promising avenues for targeted cancer therapy. Their therapeutic potential in cancer therapy is notable in many FDA-approved anticancer drugs. This review provides a comprehensive overview of the latest research from 2021 regarding novel pyrazole, pyrazoline, and fused pyrazole derivatives targeting receptor tyrosine kinases, namely: AXL, DDR, EGFR, FGFR, MET, CSF1R, RET, and VEGFR-2. This study focuses on the most active and promising candidates within each series of compounds. Key aspects covered include their cytotoxicity and enzyme inhibition results, with comparisons to reference drugs. The review also covers the molecular docking studies, highlighting critical binding interactions between the compounds and the protein kinase residues, and unveiling their molecular mechanisms of action. Structure–activity relationship analyses are also discussed, revealing the influence of structural modifications on biological activities. Furthermore, synthetic pathways for each series or key compounds are presented, offering a practical guide for researchers in the field. By integrating these elements, this review provides a solid foundation and rationale for the design, synthesis, and optimization of new pyrazole-based anticancer agents targeting receptor tyrosine kinases.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.