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

MEK and the inhibitors: from bench to bedside

(2013) Akintunde Akinleye et al.   Journal of Hematology & Oncology

Abstract 4716: A first-in-human phase 1 study to evaluate the MEK1/2 inhibitor GDC-0973 administered daily in patients with advanced solid tumors

(2012) Lee Rosen et al.   CANCER RESEARCH

Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling

(2012) Michael Röring et al.   EMBO JOURNAL

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

(2012) Robert A. Heald et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

(2012) Kenneth D. Rice et al.   ACS Medicinal Chemistry Letters

Fully Activated MEK1 Exhibits Compromised Affinity for Binding of Allosteric Inhibitors U0126 and PD0325901

(2011) Payal R. Sheth et al.   BIOCHEMISTRY

c-Raf, but Not B-Raf, Is Essential for Development of K-Ras Oncogene-Driven Non-Small Cell Lung Carcinoma

(2011) Rafael B. Blasco et al.   CANCER CELL

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

(2011) K. P. Hoeflich et al.   CANCER RESEARCH

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition

(2011) A. G. Gilmartin et al.   CLINICAL CANCER RESEARCH

Novel mitogen-activated protein kinase kinase inhibitors

(2011) Mark S Chapman et al.   EXPERT OPINION ON INVESTIGATIONAL DRUGS

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

(2010) Sonja J. Heidorn et al.   CELL

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

(2010) Poulikos I. Poulikakos et al.   NATURE

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

(2010) Georgia Hatzivassiliou et al.   NATURE

Preclinical disposition and pharmacokinetics-pharmacodynamic modeling of biomarker response and tumour growth inhibition in xenograft mouse models of G-573, a MEK inhibitor

(2010) Edna F. Choo et al.   XENOBIOTICA

V600EBRAF is associated with disabled feedback inhibition of RAF-MEK signaling and elevated transcriptional output of the pathway

(2009) C. A. Pratilas et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BRAF V600E Disrupts AZD6244-Induced Abrogation of Negative Feedback Pathways between Extracellular Signal-Regulated Kinase and Raf Proteins

(2008) B. B. Friday et al.   CANCER RESEARCH

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

(2008) Jeffrey A Engelman et al.   NATURE MEDICINE

Understanding organofluorine chemistry. An introduction to the C–F bond

(2007) David O'Hagan   CHEMICAL SOCIETY REVIEWS