Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

Georgia Hatzivassiliou, Jacob R. Haling, Huifen Chen, +18

Nature

OncologyMedicineReceptor Tyrosine KinaseCancer GeneticsRadiation Oncology +4

Intermittent Administration of MEK Inhibitor GDC-0973 plus PI3K Inhibitor GDC-0941 Triggers Robust Apoptosis and Tumor Growth Inhibition

Klaus P. Hoeflich, Mark Merchant, Christine Orr, +11

Cancer Research

Chemoprevention StrategyApoptosisCell DeathMek Inhibitor Gdc-0973Tumor Biology +17

Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events

Jinfeng Liu, William Lee, Zhaoshi Jiang, +31

Genome Research

EngineeringGeneticsAdditional ExonGenomicsSplicing Variant +18

Antitumor Efficacy of the Novel RAF Inhibitor GDC-0879 Is Predicted by BRAFV600E Mutational Status and Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Suppression

Klaus P. Hoeflich, Sylvia Herter, Janet Tien, +12

Cancer Research

Tumor BiologyMelanoma TumorsOncogenic ActivationNovel TherapyMedicine +12

Discovery of (<i>S</i>)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1<i>H</i>-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1<i>H</i>)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Development

James F. Blake, Michael Burkard, Jocelyn Chan, +28

Journal of Medicinal Chemistry

Erk Kinase ActivityCellular PharmacologyTumor BiologyPre-clinical PharmacologyMolecular Pharmacology +18

Combined MEK and ERK inhibition overcomes therapy-mediated pathway reactivation in RAS mutant tumors

Mark Merchant, John G. Moffat, Gabriele Schaefer, +20

PLoS ONE

Erk InhibitionCancer BiologyBraf Mutant ModelsTumor BiologySignaling Pathway +14

Clinical responses to ERK inhibition in BRAF V600E-mutant colorectal cancer predicted using a computational model

Daniel C. Kirouac, Gabriele Schaefer, Jocelyn Chan, +7

npj Systems Biology and Applications

Phosphoproteomic characterization of DNA damage response in melanoma cells following MEK/PI3K dual inhibition

Donald S. Kirkpatrick, Daisy Bustos, Taner Dogan, +8

Proceedings of the National Academy of Sciences

Molecular BiologyCell DeathCancer BiologyMelanoma CellsTumor Biology +19

Role of P-Glycoprotein on the Brain Penetration and Brain Pharmacodynamic Activity of the MEK Inhibitor Cobimetinib

Edna F. Choo, Justin Q. Ly, Jocelyn Chan, +5

Molecular Pharmaceutics

Cobimetinib PharmacokineticsBrain PenetrationPharmacotherapyGliomaTumor Biology +19

Discovery of Novel Allosteric Mitogen-Activated Protein Kinase Kinase (MEK) 1,2 Inhibitors Possessing Bidentate Ser212 Interactions

Robert A. Heald, Philip S. Jackson, Pascal Savy, +15

Journal of Medicinal Chemistry

Drug TargetEngineeringBidentate Ser212 InteractionsMedicinal ChemistrySignaling Pathway +14