Structural Analysis of DFG-in and DFG-out Dual Src-Abl Inhibitors Sharing a Common Vinyl Purine Template

-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations

Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. ...

Studies of N(9)-arenthenyl purines as novel DFG-in and DFG-out dual Src/Abl inhibitors using 3D-QSAR, docking and molecular dynamics simulations.

Recently, the development of Src/Abl (c-Src/Bcr-Abl tyrosine kinases) dual inhibitors has attracted considerable attention from the research community for treatment of malignancies. In order to explore the different structural features impacting the Src and Abl inhibitory activities of N(9)-arenethenyl purines and to investigate the molecular mechanisms of ligand-receptor interactions, a molecu...

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase...

Computational Study of the “DFG-Flip” Conformational Transition in c-Abl and c-Src Tyrosine Kinases

Protein tyrosine kinases are crucial to cellular signaling pathways regulating cell growth, proliferation, metabolism, differentiation, and migration. To maintain normal regulation of cellular signal transductions, the activities of tyrosine kinases are also highly regulated. The conformation of a three-residue motif Asp-Phe-Gly (DFG) near the N-terminus of the long "activation" loop covering t...

Anr - Dfg 2008