Allosteric modulators of MEK1: drug design and discovery

Ras Conformational Ensembles, Allostery, and Signaling

(2016) Shaoyong Lu et al.   CHEMICAL REVIEWS

ASBench: benchmarking sets for allosteric discovery: Fig. 1.

(2015) Wenkang Huang et al.   BIOINFORMATICS

Enhancing therapeutic efficacy of the MEK inhibitor, MEK162, by blocking autophagy or inhibiting PI3K/Akt signaling in human lung cancer cells

(2015) Weilong Yao et al.   CANCER LETTERS

GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site

(2015) Shaoyong Lu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

ASD v3.0: unraveling allosteric regulation with structural mechanisms and biological networks

(2015) Qiancheng Shen et al.   NUCLEIC ACIDS RESEARCH

The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation

(2015) Shaoyong Lu et al.   STRUCTURE

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

(2015) Ludovica Ciuffreda et al.   NEOPLASIA

Allosteric MEK1/2 Inhibitor Refametinib (BAY 86-9766) in Combination with Sorafenib Exhibits Antitumor Activity in Preclinical Murine and Rat Models of Hepatocellular Carcinoma

(2015) Roberta Schmieder et al.   NEOPLASIA

Preclinical efficacy of MEK inhibition in Nras-mutant AML

(2014) M. R. Burgess et al.   BLOOD

Recent computational advances in the identification of allosteric sites in proteins

(2014) Shaoyong Lu et al.   DRUG DISCOVERY TODAY

A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas

(2014) Jeffrey R. Infante et al.   EUROPEAN JOURNAL OF CANCER

Novel approaches for targeting kinases: allosteric inhibition, allosteric activation and pseudokinases

(2014) Sandra W Cowan-Jacob et al.   Future Medicinal Chemistry

Harnessing Allostery: A Novel Approach to Drug Discovery

(2014) Shaoyong Lu et al.   MEDICINAL RESEARCH REVIEWS

The clinical development of MEK inhibitors

(2014) Yujie Zhao et al.   Nature Reviews Clinical Oncology

A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours

(2013) D W Bowles et al.   BRITISH JOURNAL OF CANCER

Allostery in Disease and in Drug Discovery

(2013) Ruth Nussinov et al.   CELL

Multicenter Phase I Trial of the Mitogen-Activated Protein Kinase 1/2 Inhibitor BAY 86-9766 in Patients with Advanced Cancer

(2013) C. D. Weekes et al.   CLINICAL CANCER RESEARCH

Phase II Trial of MEK Inhibitor Selumetinib (AZD6244, ARRY-142886) in Patients with BRAFV600E/K-Mutated Melanoma

(2013) F. Catalanotti et al.   CLINICAL CANCER RESEARCH

Cancer therapeutics: Targeting the apoptotic pathway

(2013) Khurum H. Khan et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study

(2013) Paolo A Ascierto et al.   LANCET ONCOLOGY

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

(2013) Georgia Hatzivassiliou et al.   NATURE

A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets

(2012) Joost CM Uitdehaag et al.   BRITISH JOURNAL OF PHARMACOLOGY

Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors

(2012) S. Leijen et al.   CLINICAL CANCER RESEARCH

The Different Ways through Which Specificity Works in Orthosteric and Allosteric Drugs

(2012) Ruth Nussinov et al.   CURRENT PHARMACEUTICAL DESIGN

New Directions in Targeting Protein Kinases: Focusing Upon True Allosteric and Bivalent Inhibitors

(2012) Vandana Lamba et al.   CURRENT PHARMACEUTICAL DESIGN

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

Engineering human MEK-1 for structural studies: A case study of combinatorial domain hunting

(2012) Christoph Meier et al.   JOURNAL OF STRUCTURAL BIOLOGY

Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial

(2012) Gerald S Falchook et al.   LANCET ONCOLOGY

Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial

(2012) Jeffrey R Infante et al.   LANCET ONCOLOGY

Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

(2012) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

ERK1/2 MAP kinases: Structure, function, and regulation

(2012) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Fluorophore Labeled Kinase Detects Ligands That Bind within the MAPK Insert of p38α Kinase

(2012) Matthäus Getlik et al.   PLoS One

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

Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer

(2011) Qing Dong et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and synthesis of novel allosteric MEK inhibitor CH4987655 as an orally available anticancer agent

(2011) Yoshiaki Isshiki et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Fused thiophene derivatives as MEK inhibitors

(2011) Victoria E. Laing et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Pilot study of PD-0325901 in previously treated patients with advanced melanoma, breast cancer, and colon cancer

(2011) Peter D. Boasberg et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

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

The secret life of kinases: functions beyond catalysis

(2011) Jens Rauch et al.   Cell Communication and Signaling

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

(2011) J. M. Kirkwood et al.   CLINICAL 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

LIM kinases are attractive targets with many macromolecular partners and only a few small molecule regulators

(2011) Fabrizio Manetti   MEDICINAL RESEARCH REVIEWS

Comprehensive analysis of kinase inhibitor selectivity

(2011) Mindy I Davis et al.   NATURE BIOTECHNOLOGY

Allo-network drugs: harnessing allostery in cellular networks

(2011) Ruth Nussinov et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Proteus in the World of Proteins: Conformational Changes in Protein Kinases

(2010) Matthias Rabiller et al.   ARCHIV DER PHARMAZIE

Structure-based design and synthesis of pyrrole derivatives as MEK inhibitors

(2010) Michael B. Wallace et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Tanzanian malignant lymphomas: WHO classification, presentation, ploidy, proliferation and HIV/EBV association

(2010) Amos R Mwakigonja et al.   BMC CANCER

Treatment of Hemodialyzed Patients with Sunitinib in Renal Cell Carcinoma

(2010) Silvia Park et al.   CHEMOTHERAPY

A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

(2010) E. B. Haura et al.   CLINICAL CANCER RESEARCH

The First-in-Human Study of the Hydrogen Sulfate (Hyd-Sulfate) Capsule of the MEK1/2 Inhibitor AZD6244 (ARRY-142886): A Phase I Open-Label Multicenter Trial in Patients with Advanced Cancer

(2010) U. Banerji et al.   CLINICAL CANCER RESEARCH

BRAF mutation-selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic-potentiated synergism with the mTOR inhibitor temsirolimus

(2010) Dingxie Liu et al.   INTERNATIONAL JOURNAL OF CANCER

A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens

(2010) Jaafar Bennouna et al.   INVESTIGATIONAL NEW DRUGS

Adjuvant Gemcitabine Alone Versus Gemcitabine-Based Chemoradiotherapy After Curative Resection for Pancreatic Cancer: A Randomized EORTC-40013-22012/FFCD-9203/GERCOR Phase II Study

(2010) Jean-Luc Van Laethem et al.   JOURNAL OF CLINICAL ONCOLOGY

A Phase II, Open-Label, Randomized Study to Assess the Efficacy and Safety of AZD6244 (ARRY-142886) Versus Pemetrexed in Patients with Non-small Cell Lung Cancer Who Have Failed One or Two Prior Chemotherapeutic Regimens

(2010) John D. Hainsworth et al.   Journal of Thoracic Oncology

MEK Inhibitor PD0325901 Significantly Reduces the Growth of Papillary Thyroid Carcinoma Cells In vitro and In vivo

(2010) Y. C. Henderson et al.   MOLECULAR CANCER THERAPEUTICS

The role of signaling pathways in the development and treatment of hepatocellular carcinoma

(2010) S Whittaker et al.   ONCOGENE

Crystal Structures of MEK1 Binary and Ternary Complexes with Nucleotides and Inhibitors

(2009) Thierry O. Fischmann et al.   BIOCHEMISTRY

RDEA119/BAY 869766: A Potent, Selective, Allosteric Inhibitor of MEK1/2 for the Treatment of Cancer

(2009) C. Iverson et al.   CANCER RESEARCH

The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Oral Doses of CH4987655 in Healthy Volunteers: Target Suppression Using a Biomarker

(2009) L. Lee et al.   CLINICAL CANCER RESEARCH

The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901

(2008) Stephen D. Barrett et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor AZD6244 (ARRY-142886) Induces Growth Arrest in Melanoma Cells and Tumor Regression When Combined with Docetaxel

(2008) N. K. Haass et al.   CLINICAL CANCER RESEARCH

Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study

(2008) Ezra E.W. Cohen et al.   JOURNAL OF CLINICAL ONCOLOGY

Allosteric regulation and catalysis emerge via a common route

(2008) Nina M Goodey et al.   Nature Chemical Biology