2yfx | pdb_00002yfx

Structure of L1196M Mutant Anaplastic Lymphoma Kinase in Complex with Crizotinib

spinqualitylabelsall models 2yfx, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2yfx is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: VGH Related: 2xp2, 2yhv, 4anl, 4anq, 4ccb, 4ccu, 4cd0 Activity: Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Crizotinib (1), an ALK receptor tyrosine kinase inhibitor approved by the FDA in 2011, is efficacious in ALK and ROS positive patients. Under pressure of crizotinib treatment, point mutations arise in the kinase domain of ALK, resulting in resistance and progressive disease. The successful application of both structure-based and lipophilic-efficiency-focused drug design resulted in aminopyridine 8e which was potent across a broad panel of engineered ALK mutant cell lines, showed suitable pre-clinical PK and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M). The design of potent and selective inhibitors to overcome clinical ALK mutations resistant to crizotinib.,Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook A, Cui JJ, Dack KN, Deal JG, Deng YL, Dinh DM, Engstrom LD, He M, Hoffman J, Hoffman RL, Shen H, Johnson P, Kania RS, Lam H, Lam JL, Le P, Li Q, Lingardo L, Liu W, West Lu M, McTigue MA, Palmer CL, Richardson PF, Sach NW, Smeal T, Smith GL, Stewart AE, Timofeevski SL, Tsaparikos K, Wang H, Zhu H, Zhu J, Zou HY, Edwards M J Med Chem. 2014 Jan 16. PMID:24432909 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Tyrosine kinase

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