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Nature, ISSN 0028-0836, 03/2010, Volume 464, Issue 7287, pp. 431 - 435
Activating mutations in KRAS and BRAF are found in more than 30% of all human tumours and 40% of melanoma, respectively, thus targeting this pathway could have... 
SELECTIVE INHIBITOR | POTENT | EFFICACY | PHOSPHORYLATION | MULTIDISCIPLINARY SCIENCES | IN-VIVO | C-RAF | HETERODIMERIZATION | B-RAF | PROTEIN-KINASE KINASE | CANCER | Neoplasms - metabolism | ras Proteins - genetics | Proto-Oncogene Proteins p21(ras) | Diphenylamine - pharmacology | raf Kinases - antagonists & inhibitors | Humans | Protein Multimerization | ras Proteins - metabolism | Protein Transport - drug effects | Extracellular Signal-Regulated MAP Kinases - metabolism | raf Kinases - metabolism | Diphenylamine - analogs & derivatives | Mitogen-Activated Protein Kinase Kinases - metabolism | Adenosine Triphosphate - metabolism | Indoles - pharmacology | Benzamides - pharmacology | Cell Membrane - metabolism | raf Kinases - genetics | Cell Membrane - drug effects | Proto-Oncogene Proteins B-raf - metabolism | Proto-Oncogene Proteins B-raf - chemistry | Pyrazoles - pharmacology | Protein Structure, Tertiary | Proto-Oncogene Proteins - metabolism | Cell Line | Indenes - pharmacology | raf Kinases - chemistry | Proto-Oncogene Proteins c-raf - genetics | Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors | Neoplasms - enzymology | Proto-Oncogene Proteins - genetics | Enzyme Activation - drug effects | Sulfonamides - pharmacology | Proto-Oncogene Proteins c-raf - metabolism | Neoplasms - drug therapy | Proto-Oncogene Proteins B-raf - antagonists & inhibitors | Xenograft Model Antitumor Assays | Animals | MAP Kinase Signaling System - drug effects | Protein Kinase Inhibitors - therapeutic use | Proto-Oncogene Proteins B-raf - genetics | Proto-Oncogene Proteins c-raf - deficiency | Cell Proliferation - drug effects | Mice | Protein Kinase Inhibitors - pharmacology | Neoplasms - pathology | Ras genes | Growth | Physiological aspects | Cellular signal transduction | Genetic aspects | Research | Mitogen-activated protein kinases | Competition | Clinical trials | Enzymes | Kinases | Index Medicus | Proteins | Cellular | Inhibitors | Pathways | Tumours | Signalling | Dimerization
Journal Article
Nature, ISSN 0028-0836, 03/2010, Volume 464, Issue 7287, pp. 427 - 430
Tumours with mutant BRAF are dependent on the RAF–MEK–ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK... 
SELECTIVE INHIBITOR | ACTIVATION | MELANOMA | MECHANISM | MULTIDISCIPLINARY SCIENCES | SENSITIVITY | HETERODIMERIZATION | KINASE INHIBITOR | B-RAF | CRAF | ONCOGENIC BRAF | Neoplasms - metabolism | ras Proteins - genetics | Phosphorylation | raf Kinases - antagonists & inhibitors | Humans | Protein Multimerization | Transcriptional Activation - drug effects | ras Proteins - metabolism | Extracellular Signal-Regulated MAP Kinases - metabolism | raf Kinases - metabolism | Mitogen-Activated Protein Kinase Kinases - metabolism | Neoplasms - genetics | Adenosine Triphosphate - metabolism | Indoles - pharmacology | raf Kinases - genetics | Proto-Oncogene Proteins B-raf - metabolism | Proto-Oncogene Proteins B-raf - chemistry | Cell Line | raf Kinases - chemistry | Catalytic Domain | Neoplasms - enzymology | Enzyme Activation - drug effects | Sulfonamides - pharmacology | Neoplasms - drug therapy | Proto-Oncogene Proteins B-raf - antagonists & inhibitors | Animals | MAP Kinase Signaling System - drug effects | Models, Biological | Protein Kinase Inhibitors - therapeutic use | Proto-Oncogene Proteins B-raf - genetics | Cell Line, Tumor | Protein Binding | Mice | Protein Kinase Inhibitors - pharmacology | Protein Kinase Inhibitors - metabolism | Care and treatment | Enzyme inhibitors | Gene mutations | Cellular signal transduction | Genetic aspects | Research | Health aspects | Cancer | Proteins | Competition | Drugs | Mutation | Kinases | Tumors | Index Medicus
Journal Article
Nature, ISSN 0028-0836, 10/2017, Volume 550, Issue 7674, pp. 133 - 136
Targeted BRAF inhibition (BRAFi) and combined BRAF and MEK inhibition (BRAFi and MEKi) therapies have markedly improved the clinical outcomes of patients with... 
METASTATIC MELANOMA | MEK | EPITHELIAL-CELLS | PHOSPHORYLATION | PATHWAY | RAF | P21-ACTIVATED-KINASE-1 | MULTIDISCIPLINARY SCIENCES | KINASE | MECHANISMS | THERAPIES | TOR Serine-Threonine Kinases - metabolism | Apoptosis - drug effects | Humans | p21-Activated Kinases - antagonists & inhibitors | Melanoma - enzymology | JNK Mitogen-Activated Protein Kinases - metabolism | Mitogen-Activated Protein Kinase Kinases - metabolism | Melanoma - genetics | Proto-Oncogene Proteins c-raf - chemistry | Female | beta Catenin - chemistry | Phosphorylation - drug effects | p21-Activated Kinases - genetics | JNK Mitogen-Activated Protein Kinases - chemistry | Enzyme Activation - drug effects | p21-Activated Kinases - metabolism | beta Catenin - metabolism | Proto-Oncogene Proteins c-raf - metabolism | Mitogen-Activated Protein Kinase Kinases - chemistry | Drug Resistance, Neoplasm - genetics | Animals | MAP Kinase Signaling System - drug effects | Mitogen-Activated Protein Kinases - antagonists & inhibitors | Signal Transduction - drug effects | Proto-Oncogene Proteins B-raf - genetics | Melanoma - drug therapy | Cell Line, Tumor | Mice | Protein Kinase Inhibitors - pharmacology | Mutation | Drug Resistance, Neoplasm - drug effects | Melanoma | Physiological aspects | Cellular signal transduction | Drug resistance | Observations | Health aspects | Mitogen-activated protein kinases | TOR protein | Therapy | Phosphorylation | Activation | Metastasis | Drug development | Kinases | Cancer therapies | Metastases | Proteins | β-catenin | Signal transduction | Inhibition | Extracellular signal-regulated kinase | MAP kinase | JNK protein | Patients | Signaling | Protein arrays | Molecular modelling | Biopsy | Cell lines | Apoptosis | Index Medicus
Journal Article
Nature chemical biology, ISSN 1552-4450, 10/2014, Volume 10, Issue 10, pp. 853 - 860
Activation of the ERK pathway is a hallmark of cancer, and targeting of upstream signaling partners led to the development of approved drugs. Recently,... 
POLY(ADP-RIBOSE) POLYMERASE | RAF INHIBITION | BIOCHEMISTRY & MOLECULAR BIOLOGY | DNA-DAMAGE | ACQUIRED-RESISTANCE | MAP KINASE ERK2 | BRAF | CONFORMATION | MEK INHIBITORS | SELECTIVITY | DISCOVERY | Humans | Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors | Gene Expression Regulation, Neoplastic | Intracellular Signaling Peptides and Proteins - metabolism | Piperazines - chemistry | Mitogen-Activated Protein Kinase 1 - chemistry | Enzyme Inhibitors - chemistry | Mitogen-Activated Protein Kinase 1 - genetics | Mitogen-Activated Protein Kinase 8 - genetics | Antineoplastic Agents - pharmacology | Mitogen-Activated Protein Kinase 3 - chemistry | Binding Sites | Intracellular Signaling Peptides and Proteins - genetics | Protein-Serine-Threonine Kinases - metabolism | Protein Structure, Tertiary | Recombinant Proteins - metabolism | Gene Expression | Indazoles - chemistry | Mitogen-Activated Protein Kinase 3 - genetics | Protein Structure, Secondary | Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors | Mitogen-Activated Protein Kinase 8 - chemistry | Mitogen-Activated Protein Kinase 8 - metabolism | Enzyme Inhibitors - pharmacology | Protein-Serine-Threonine Kinases - genetics | Recombinant Proteins - chemistry | Recombinant Proteins - genetics | Antineoplastic Agents - chemistry | Piperazines - pharmacology | Indazoles - pharmacology | MAP Kinase Signaling System - drug effects | Mitogen-Activated Protein Kinase 3 - metabolism | Intracellular Signaling Peptides and Proteins - chemistry | Cell Line, Tumor | Protein Binding | Protein-Serine-Threonine Kinases - chemistry | Kinetics | Mitogen-Activated Protein Kinase 1 - metabolism | Signal transduction | Binding sites | Pharmaceutical sciences | Cancer | Index Medicus
Journal Article
Journal Article
Nature, ISSN 0028-0836, 2014, Volume 510, Issue 7504, pp. 283 - 287
Deregulation of lysine methylation signalling has emerged as a common aetiological factor in cancer pathogenesis, with inhibitors of several histone lysine... 
LUNG-CANCER | ACTIVATION | PROTEIN | K-RAS | MULTIDISCIPLINARY SCIENCES | MOUSE MODEL | KINASE | PANCREATIC INTRAEPITHELIAL NEOPLASIA | GROWTH-FACTOR | HISTONE METHYLTRANSFERASE | PROGRESSION | Adenocarcinoma - pathology | Pancreatic Neoplasms - metabolism | Adenocarcinoma of Lung | Humans | Lung Neoplasms - metabolism | Lung Neoplasms - pathology | Oncogene Protein p21(ras) - metabolism | MAP Kinase Kinase Kinases - chemistry | Adenocarcinoma - metabolism | Cell Transformation, Neoplastic - genetics | MAP Kinase Kinase Kinase 2 - chemistry | Adenocarcinoma - genetics | Lysine - metabolism | Disease Models, Animal | Lung Neoplasms - genetics | MAP Kinase Kinase Kinase 2 - metabolism | Lung Neoplasms - enzymology | Protein Phosphatase 2 - antagonists & inhibitors | Signal Transduction | Pancreatic Neoplasms - pathology | Adenocarcinoma - enzymology | Pancreatic Neoplasms - enzymology | Pancreatic Neoplasms - genetics | MAP Kinase Kinase Kinases - metabolism | Cell Transformation, Neoplastic - metabolism | Proto-Oncogene Proteins A-raf - metabolism | Animals | Histone-Lysine N-Methyltransferase - metabolism | Protein Phosphatase 2 - metabolism | Cell Line, Tumor | Mice | Cell Transformation, Neoplastic - pathology | Methylation | Mitogen-Activated Protein Kinases - metabolism | Oncogene Protein p21(ras) - genetics | Physiological aspects | Research | Lysine | Oncology, Experimental | Cancer | DNA methylation | Peptides | Kinases | Rodents | Tumors | Index Medicus
Journal Article
Nature, ISSN 0028-0836, 02/2018, Volume 554, Issue 7693, pp. 549 - 553
Journal Article
Nature, ISSN 0028-0836, 08/2016, Volume 537, Issue 7618, pp. 112 - 116
Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted... 
ACTIVATION | PROTEIN | MEK INHIBITION | MECHANISM | KINASE SUPPRESSOR | COMPLEX REVEALS | MULTIDISCIPLINARY SCIENCES | C-ELEGANS | BRAF | GENE ENCODES | SCAFFOLD | Neoplasms - metabolism | ras Proteins - genetics | Humans | Protein Conformation - drug effects | ras Proteins - metabolism | Enzyme Stability - drug effects | raf Kinases - metabolism | Mitogen-Activated Protein Kinase Kinases - metabolism | Neoplasms - genetics | Pyrimidinones - pharmacology | Phosphorylation - drug effects | Protein-Serine-Threonine Kinases - metabolism | Allosteric Regulation - drug effects | Cell Line | Oncogenes - genetics | raf Kinases - chemistry | Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors | Protein-Serine-Threonine Kinases - genetics | ras Proteins - antagonists & inhibitors | Models, Molecular | Neoplasms - enzymology | Neoplasms - drug therapy | Mitogen-Activated Protein Kinase Kinases - chemistry | MAP Kinase Signaling System - drug effects | Alleles | Oncogenes - drug effects | Protein Binding | Protein-Serine-Threonine Kinases - chemistry | Mutation | Quinazolines - pharmacology | Protein Multimerization - drug effects | Pyridones - pharmacology | Physiological aspects | Ras genes | Care and treatment | Phosphotransferases | Methods | Cancer | Signal transduction | Phosphorylation | Genes | Ligands | Kinases | Crystal structure | Index Medicus
Journal Article
Cell, ISSN 0092-8674, 04/2016, Volume 165, Issue 3, pp. 643 - 655
Oncogenic activation of genes via point mutations occurs in 20%–30% of human cancers. The development of effective RAS inhibitors has been challenging,... 
rigosertib | RAS-binding domain | PI3K | MAPK | RAS | RAF | POINT MUTATIONS | BLADDER-CARCINOMA ONCOGENE | MUTANT | SELECTIVE INHIBITOR | ACTIVATION | PHOSPHORYLATION | BIOCHEMISTRY & MOLECULAR BIOLOGY | IN-VIVO | KINASE | BINDING | TRANSFORMING PROPERTIES | CELL BIOLOGY | Glycine - analogs & derivatives | Phosphorylation | Humans | Molecular Sequence Data | ras Proteins - metabolism | Crystallography, X-Ray | Proto-Oncogene Proteins - chemistry | Sulfones - pharmacology | MAP Kinase Signaling System | Cell Cycle Proteins - chemistry | Pancreatic Neoplasms - drug therapy | Glycine - chemistry | Sulfones - chemistry | Nuclear Magnetic Resonance, Biomolecular | Dimerization | Glycine - administration & dosage | Protein-Serine-Threonine Kinases - metabolism | Proto-Oncogene Proteins B-raf - metabolism | Proto-Oncogene Proteins B-raf - chemistry | Proto-Oncogene Proteins - metabolism | Amino Acid Sequence | RNA-Binding Proteins - chemistry | Cell Cycle Proteins - metabolism | Models, Molecular | Sequence Alignment | Animals | Glycine - pharmacology | Signal Transduction - drug effects | Mice, Nude | Mice | Protein-Serine-Threonine Kinases - chemistry | Cell Transformation, Neoplastic - drug effects | RNA-Binding Proteins - metabolism | Sulfones - administration & dosage | Proteins | Medical colleges | Gene mutations | Protein binding | Jewish schools | Phosphotransferases | Index Medicus
Journal Article