Aim:To design and synthesize a novel class of antitumor agents,featuring the 3,5-substituted indolin-2-one framework.Methods:Based on enzyme binding fea-tures of(Z)-SU5402,introducing a β-pyrrole group at the 3-position of the indolin-2-one core,a series of novel 3,5-substituted indolin-2-ones were designed andsynthesized.Four human carcinoma cell lines of A-43l,A-549,MDA-MB-468,and Autosomal Dominant Polycystic Kidney disease were chosen for the cellproliferation assay.Results:Twenty new compounds(1a-t)with E configurationhave been designed,synthesized and bioassayed.Their structural features weredetermined by nuclear magnetic resonance(NMR)spectra,low-and high-resolu-tion mass spectra,and confirmed by X-ray crystallography.Although the enzymeassay showed a weak inhibition effect against the epidermal growth factor receptor,vascular endothelial growth factor receptor,fibroblast growth factor receptor andplatelet-derived growth factor receptor tyrosine kinases,the cell-based antitumoractivity was promising.Compounds 1 g and lh showed higher inhibitory activitytoward the A-549 and MDA-MB-468 cell lines with IC_(50)of 0.065-9.4 μmol/L.Conclusion:This study provides a new template for further development ofpotent antitumor drugs. Aim: To design and synthesize novel class of antitumor agents, featuring the 3,5-substituted indolin-2-one framework. Methods: Based on enzyme binding fea- tures of (Z) -SU5402, introducing a β-pyrrole group at the 3-position of the indolin-2-one core, a series of novel 3,5-substituted indolin-2-ones were designed andsynthesized. Flow human carcinoma cell lines of A-431, A-549, MDA-MB-468 , and Autosomal Dominant Polycystic Kidney Disease were chosen for the cellproliferation assay. Results: Twenty new compounds (1a-t) with E configuration have been designed, synthesized and bioassayed. Their structural features were determined by nuclear magnetic resonance (NMR) spectra, low-and high-resolu tion mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay showed a weak inhibition effect against the epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor tyrosine kinases, the cell-based antitumor activity was promising. Compounds 1 g and lh showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC 50 (50) of 0.065-9.4 μmol / L. Conlusion: This study provides a new template for further development of potent antitumor drugs.