2E2B

Crystal structure of the c-Abl kinase domain in complex with INNO-406

Summary for 2E2B

• Entry DOI: 10.2210/pdb2e2b/pdb
• Descriptor: Proto-oncogene tyrosine-protein kinase ABL1, N-[3-(4,5'-BIPYRIMIDIN-2-YLAMINO)-4-METHYLPHENYL]-4-{[(3S)-3-(DIMETHYLAMINO)PYRROLIDIN-1-YL]METHYL}-3-(TRIFLUOROMETHYL) BENZAMIDE (3 entities in total)
• Functional Keywords: c-abl, kinase, inno-406, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton. Isoform IB: Nucleus membrane; Lipid-anchor: P00519
• Total number of polymer chains: 2
• Total formula weight: 68632.25

Authors

Horio, T.,Hamasaki, T.,Wakayama, T.,Takagaki, K.,Ohgi, T. (deposition date: 2006-11-10, release date: 2007-05-22, Last modification date: 2023-10-25)

Primary citation

Horio, T.,Hamasaki, T.,Inoue, T.,Wakayama, T.,Itou, S.,Naito, H.,Asaki, T.,Hayase, H.,Niwa, T.
Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives
Bioorg.Med.Chem.Lett., 17:2712-2717, 2007

PubMed Abstract: To investigate why 3-substituted benzamide derivatives show dual inhibition of Abl and Lyn protein tyrosine kinases, we determined their inhibitory activities against Abl and Lyn, carried out molecular modeling, and conducted a structure-activity relationship study with the aid of a newly determined X-ray structure of the Abl/Lyn dual inhibitor INNO-406 (formerly known as NS-187) bound to human Abl. We found that this series of compounds interacted with both kinases in very similar ways, so that they can inhibit both kinases effectively.

PubMed: 17376680
DOI: 10.1016/j.bmcl.2007.03.002

Experimental method

X-RAY DIFFRACTION (2.2 Å)