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Protein kinases are targets for the treatment of a number of diseases. Sunitinib malate is a type I inhibitor of tyrosine kinases and was approved as a drug in 2006. This contribution constitutes the first comprehensive analysis of the crystal structures of sunitinib malate and of complexes of sunitinib with a series of protein kinases. The high-resolution single-crystal X-ray measurement and aspherical atom databank approach served as a basis for reconstruction of the charge-density distribution of sunitinib and its protein complexes. Hirshfeld surface and topological analyses revealed a similar interaction pattern in the sunitinib malate crystal structure to that in the protein binding pockets. Sunitinib forms nine preserved bond paths corresponding to hydrogen bonds and also to the C—H...O and C—H...π contacts common to the VEGRF2, CDK2, G2, KIT and IT kinases. In general, sunitinib interacts with the studied proteins with a similar electrostatic interaction energy and can adjust its conformation to fit the binding pocket in such a way as to enhance the electrostatic interactions, e.g. hydrogen bonds in ligand–kinase complexes. Such behaviour may be responsible for the broad spectrum of action of sunitinib as a kinase inhibitor.

Supporting information

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Portable Document Format (PDF) file https://doi.org/10.1107/S1399004714002351/dz5313sup1.pdf
The supporting information contains bond distances and selected intermolecular contacts resulting from the final multipole model (S1-S3), residual density maps, normal probability plots, scale plots, selected topological parameters at BCPs, integrated atomic charges and integrated Laplacian, fractional dimension versus residual density plots for selected planes, minima and maxima of residual density for SUM as well as the results of Hirshfeld surface analysis, topological analysis of SU-PK complexes, the result of protein alignment, tables with the individual result of Ees calculation for all SU-PK complexes, three-dimensional maps of electrostatic potential mapped on van der Waals surface for the SU molecule and binding pocket of VEGFR2 and tables related to theoretical calculations.


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