Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor

Inhibitors of BRAF dimers using an allosteric site

(2020) Xiomaris M. Cotto-Rios et al.   Nature Communications

Design and Discovery of N-(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

(2019) Savithri Ramurthy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting ERK beyond the boundaries of the kinase active site in melanoma

(2019) Rachel M. Sammons et al.   MOLECULAR CARCINOGENESIS

Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma

(2019) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Current Insights of BRAF Inhibitors in Cancer

(2018) Bogos Agianian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF -mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

(2018) Reinhard Dummer et al.   LANCET ONCOLOGY

The dimer-dependent catalytic activity of RAF family kinases is revealed through characterizing their oncogenic mutants

(2018) Jimin Yuan et al.   ONCOGENE

Pharmacological Induction of RAS-GTP Confers RAF Inhibitor Sensitivity in KRAS Mutant Tumors

(2018) Ivana Yen et al.   CANCER CELL

Design and Discovery of N-(2-Methyl-5′-morpholino-6′-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3′-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide (RAF709): A Potent, Selective, and Efficacious RAF Inhibitor Targeting RAS Mutant Cancers

(2017) Gisele A. Nishiguchi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Current Development Status of MEK Inhibitors

(2017) et al.   MOLECULES

RAF inhibitor LY3009120 sensitizes RAS or BRAF mutant cancer to CDK4/6 inhibition by abemaciclib via superior inhibition of phospho-RB and suppression of cyclin D1

(2017) S-H Chen et al.   ONCOGENE

An Integrated Model of RAF Inhibitor Action Predicts Inhibitor Activity against Oncogenic BRAF Signaling

(2016) Zoi Karoulia et al.   CANCER CELL

Kinase hinge binding scaffolds and their hydrogen bond patterns

(2015) Li Xing et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers

(2015) Sheng-Bin Peng et al.   CANCER CELL

Discovery of 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea (LY3009120) as a Pan-RAF Inhibitor with Minimal Paradoxical Activation and Activity against BRAF or RAS Mutant Tumor Cells

(2015) James R. Henry et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structural Investigation of B-Raf Paradox Breaker and Inducer Inhibitors

(2015) Rohit Arora et al.   JOURNAL OF MEDICINAL CHEMISTRY

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma

(2014) Chong Sun et al.   NATURE

Targeting RAS–ERK signalling in cancer: promises and challenges

(2014) Ahmed A. Samatar et al.   NATURE REVIEWS DRUG DISCOVERY

Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

(2014) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Suzuki-Miyaura Cross-Coupling of Unprotected, Nitrogen-Rich Heterocycles: Substrate Scope and Mechanistic Investigation

(2013) M. Alexander Düfert et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

(2013) Georgia Hatzivassiliou et al.   NATURE

Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

(2013) Tara R. Rheault et al.   ACS Medicinal Chemistry Letters

Pyrazolopyridine inhibitors of B-RafV600E. Part 4: Rational design and kinase selectivity profile of cell potent type II inhibitors

(2012) Steve Wenglowsky et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Potent and Selective Aminopyrimidine-Based B-Raf Inhibitors with Favorable Physicochemical and Pharmacokinetic Properties

(2012) Simon Mathieu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent and Selective Pyrazolopyrimidine Janus Kinase 2 Inhibitors

(2012) Emily J. Hanan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations

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

Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib

(2012) Jeffrey A. Sosman et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

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

Overview of theCCP4 suite and current developments

(2011) Martyn D. Winn et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

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

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

(2011) Poulikos I. Poulikakos et al.   NATURE

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

(2011) Paul B. Chapman et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate)

(2011) Hiroyuki Abe et al.   ACS Medicinal Chemistry Letters

New Insight Puts CRAF in Sight as a Therapeutic Target: Figure 1.

(2011) Ana Paula Rebocho et al.   Cancer Discovery

Integration, scaling, space-group assignment and post-refinement

(2010) Wolfgang Kabsch   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

PHENIX: a comprehensive Python-based system for macromolecular structure solution

(2010) Paul D. Adams et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

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

(2010) Sonja J. Heidorn et al.   CELL

A New Palladium Precatalyst Allows for the Fast Suzuki−Miyaura Coupling Reactions of Unstable Polyfluorophenyl and 2-Heteroaryl Boronic Acids

(2010) Tom Kinzel et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

(2010) Georgia Hatzivassiliou et al.   NATURE

Pd-catalyzed amidation of aryl(Het) halides with tert-butyl carbamate

(2010) Lijin Qin et al.   TETRAHEDRON LETTERS

Entry into a new class of protein kinase inhibitors by pseudo ring design

(2008) Pascal Furet et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A Highly Active Catalyst for Pd-Catalyzed Amination Reactions: Cross-Coupling Reactions Using Aryl Mesylates and the Highly Selective Monoarylation of Primary Amines Using Aryl Chlorides

(2008) Brett P. Fors et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

(2008) J. Tsai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Facile Synthesis of N-Carbamoylamino Acids

(2008) Sergey Ryabukhin et al.   SYNLETT