Changqing Xu, Yang Liu and Guisen Zhao* Pages 1891 - 1919 ( 29 )
Kinases are pivotal regulators in tumorigenesis and metastasis by modulating the expression of oncogenes and the transcription of antioncogenes directly or indirectly. Correspondingly, multifarious 3-substituted indolin-2-one derivatives as selective kinase inhibitors for cancer therapy exhibited a low nanomolar activity with prominent efficacy, superior response rate and admirable tolerability. Particularly, certain 3-substituted indolin- 2-one derivatives have met the requirements for clinical trials or the pharmaceutical market. Herein, we focus on the traits of 3-substituted indolin-2-one derivatives as kinase inhibitors for cancer therapy, overview recent progress of 3-substituted indolin-2-one derivatives as kinase inhibitors for cancer therapy, analyze the selectivity for tyrosine kinases inhibitors and serine/threonine kinases inhibitors from the molecular aspects based on the molecular docking studies, summarize the structure-activity relationships (SARs) as selective kinase inhibitors and provide our perspectives for the development of 3- substituted indolin-2-one derivatives as kinase inhibitors for cancer therapy.
3-Substituted indolin-2-one, kinase inhibitor, structure-activity relationship, cancer therapy, malignancy, ATP binding.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas, Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong