5em5 | pdb_00005em5

EGFR kinase domain mutant "TMLR" with pyridone compound 2: 4-[2-(4-chlorophenyl)ethylamino]-~{N}-[4-(4-methylpiperazin-1-yl)phenyl]-2-oxidanylidene-1~{H}-pyridine-3-carboxamide

spinqualitylabelsall models 5em5, resolution 2.65Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5em5 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.65Å Ligands: 5Q2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease EGFR_HUMAN Defects in EGFR are associated with lung cancer (LNCR) [MIM:211980. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Function EGFR_HUMAN Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TGFA/TGF-alpha, amphiregulin, epigen/EPGN, BTC/betacellulin, epiregulin/EREG and HBEGF/heparin-binding EGF. Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. May also activate the NF-kappa-B signaling cascade. Also directly phosphorylates other proteins like RGS16, activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. Also phosphorylates MUC1 and increases its interaction with SRC and CTNNB1/beta-catenin. Isoform 2 may act as an antagonist of EGF action. Publication Abstract from PubMed The rapid advancement of a series of noncovalent inhibitors of T790M mutants of EGFR is discussed. The optimization of pyridone 1, a nonselective high-throughput screening hit, to potent molecules with high levels of selectivity over wtEGFR and the broader kinome is described herein. Pyridones as Highly Selective, Noncovalent Inhibitors of T790M Double Mutants of EGFR.,Bryan MC, Burdick DJ, Chan BK, Chen Y, Clausen S, Dotson J, Eigenbrot C, Elliott R, Hanan EJ, Heald R, Jackson P, La H, Lainchbury M, Malek S, Mann SE, Purkey HE, Schaefer G, Schmidt S, Seward E, Sideris S, Wang S, Yen I, Yu C, Heffron TP ACS Med Chem Lett. 2015 Dec 17;7(1):100-4. doi: 10.1021/acsmedchemlett.5b00428., eCollection 2016 Jan 14. PMID:26819674 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Epidermal growth factor receptor 3D structures

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