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Imatinib is a clinically important ATP analogue inhibitor that targets the tyrosine kinase domain of the intracellular Abl kinase and the PDGF receptor family. Imatinib has revolutionised the treatment of chronic myeloid leukaemia, which is caused by the oncogene Bcr-Abl and certain solid tumours that harbor oncogenic mutations of the PDGF receptor family. As a leading kinase inhibitor, imatinib also provides an excellent model system to investigate how changes in drug design impact biological activity, which is an important consideration for rational drug design. Herein we report a new series of imatinib derivatives that in general have greater activity against the family of PDGF receptors and poorer activity against Abl, as a result of modifications of the phenyl and N-methylpiperazine rings. These new compounds provide a platform for further drug development against the therapeutically important PDGF receptor family and they also provide insight into the engineering of drugs with altered biological activity.

Original publication




Journal article



Publication Date





130 - 139


Animals, Antineoplastic Agents, Benzamides, Binding Sites, Cell Line, Tumor, Computer Simulation, Drug Design, Fusion Proteins, bcr-abl, Humans, Imatinib Mesylate, K562 Cells, Mice, Phosphorylation, Piperazines, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-kit, Pyrimidines, Receptor, Macrophage Colony-Stimulating Factor, Receptors, Platelet-Derived Growth Factor, Substrate Specificity