Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors.

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Lu S, Luo Q, Hao X, Li X, Ji L, Zheng W, Wang F

Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors.

Bioorg Med Chem Lett. 2011 Dec 1;21(23):6964-8. doi: 10.1016/j.bmcl.2011.09.127. Epub 2011 Oct 7.

PubMed ID

22033461 [ View in PubMed

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Abstract

Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virtual screening method developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking. The docking results are consistent with the inhibitory potency of the compounds characterized by MS method. And the H-bonds between imatinib analogs and Thr315 and Met318 residues in Abl kinase are shown to be crucial for achieving accurate poses and high binding affinities for the ATP-competitive kinase inhibitors.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Imatinib	Tyrosine-protein kinase ABL1	IC 50 (nM)	234	N/A	N/A	Details