Entry Database : PDB / ID : 6n0p Structure visualization Downloads & linksTitle BRAF in complex with N-(3-(2-(2-hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide (LXH254) ComponentsSerine/threonine-protein kinase B-raf Details Keywords transferase/transferase inhibitor / Raf / bRaf / cRaf / CRAF kinase / Serine threonine protein / TRANSFERASE / transferase-transferase inhibitor complexFunction / homology Function and homology informationFunction Domain/homology Component
CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / head morphogenesis / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process ... CD4-positive, alpha-beta T cell differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / head morphogenesis / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / mitogen-activated protein kinase kinase binding / regulation of T cell differentiation / Negative feedback regulation of MAPK pathway / positive regulation of axonogenesis / Frs2-mediated activation / stress fiber assembly / positive regulation of axon regeneration / face development / synaptic vesicle exocytosis / somatic stem cell population maintenance / MAP kinase kinase activity / thyroid gland development / MAP kinase kinase kinase activity / negative regulation of endothelial cell apoptotic process / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of stress fiber assembly / response to cAMP / cellular response to calcium ion / ERK1 and ERK2 cascade / substrate adhesion-dependent cell spreading / cellular response to nerve growth factor stimulus / thymus development / long-term synaptic potentiation / animal organ morphogenesis / RAF activation / Spry regulation of FGF signaling / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / visual learning / epidermal growth factor receptor signaling pathway / response to peptide hormone / Negative regulation of MAPK pathway / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / MAPK cascade / Signaling by BRAF and RAF1 fusions / cellular response to xenobiotic stimulus / positive regulation of peptidyl-serine phosphorylation / presynapse / T cell receptor signaling pathway / regulation of cell population proliferation / cell body / T cell differentiation in thymus / scaffold protein binding / negative regulation of neuron apoptotic process / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / protein kinase activity / neuron projection / protein phosphorylation / intracellular membrane-bounded organelle / protein serine kinase activity / protein serine/threonine kinase activity / calcium ion binding / positive regulation of gene expression / protein-containing complex binding / negative regulation of apoptotic process / mitochondrion / ATP binding / identical protein binding / nucleus / plasma membrane / cytosol Similarity search - Function Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) ... Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Ubiquitin-like domain superfamily / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / Resolution : 2.37 Å DetailsAuthors Mamo, M. / Appleton, B.A. CitationJournal : J.Med.Chem. / Year : 2020Title: Design and Discovery ofN-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor ... Title : Design and Discovery ofN-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic.Authors: Ramurthy, S. / Taft, B.R. / Aversa, R.J. / Barsanti, P.A. / Burger, M.T. / Lou, Y. / Nishiguchi, G.A. / Rico, A. / Setti, L. / Smith, A. / Subramanian, S. / Tamez, V. / Tanner, H. / Wan, L. ... Authors : Ramurthy, S. / Taft, B.R. / Aversa, R.J. / Barsanti, P.A. / Burger, M.T. / Lou, Y. / Nishiguchi, G.A. / Rico, A. / Setti, L. / Smith, A. / Subramanian, S. / Tamez, V. / Tanner, H. / Wan, L. / Hu, C. / Appleton, B.A. / Mamo, M. / Tandeske, L. / Tellew, J.E. / Huang, S. / Yue, Q. / Chaudhary, A. / Tian, H. / Iyer, R. / Hassan, A.Q. / Mathews Griner, L.A. / La Bonte, L.R. / Cooke, V.G. / Van Abbema, A. / Merritt, H. / Gampa, K. / Feng, F. / Yuan, J. / Mishina, Y. / Wang, Y. / Haling, J.R. / Vaziri, S. / Hekmat-Nejad, M. / Polyakov, V. / Zang, R. / Sethuraman, V. / Amiri, P. / Singh, M. / Sellers, W.R. / Lees, E. / Shao, W. / Dillon, M.P. / Stuart, D.D. History Deposition Nov 7, 2018 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Sep 4, 2019 Provider : repository / Type : Initial releaseRevision 1.1 Mar 18, 2020 Group : Database references / Category : citationItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation.year Revision 1.2 Mar 13, 2024 Group : Data collection / Database references / Category : chem_comp_atom / chem_comp_bond / database_2Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession
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