Live-cell target engagement of allosteric MEKi on MEK–RAF/KSR–14-3-3 complexes

Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib

(2023) Emre Tkacik et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

BRAF Mutations: The Discovery of Allele- and Lineage-Specific Differences

(2022) Aphrothiti J. Hanrahan et al.   CANCER RESEARCH

Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding

(2022) Juliana A. Martinez Fiesco et al.   Nature Communications

A Structure Is Worth a Thousand Words: New Insights for RAS and RAF Regulation

(2022) Dhirendra K. Simanshu et al.   Cancer Discovery

Targeting pan-essential genes in cancer: challenges and opportunities

(2021) Liang Chang et al.   CANCER CELL

KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation

(2021) Timothy H. Tran et al.   Nature Communications

Clinical acquired resistance to KRASG12C inhibition through a novel KRAS switch-II pocket mutation and polyclonal alterations converging on RAS-MAPK reactivation

(2021) Noritaka Tanaka et al.   Cancer Discovery

Acquired Resistance to KRASG12C Inhibition in Cancer

(2021) Mark M. Awad et al.   NEW ENGLAND JOURNAL OF MEDICINE

Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation

(2021) Gonzalo L. Gonzalez-Del Pino et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Diverse alterations associated with resistance to KRAS(G12C) inhibition

(2021) Yulei Zhao et al.   NATURE

Negative regulation of RAF kinase activity by ATP is overcome by 14-3-3-induced dimerization

(2020) Nicholas P. D. Liau et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

The Frequency of Ras Mutations in Cancer

(2020) Ian A. Prior et al.   CANCER RESEARCH

Quantifying CDK inhibitor selectivity in live cells

(2020) Carrow I. Wells et al.   Nature Communications

RAS-targeted therapies: is the undruggable drugged?

(2020) Amanda R. Moore et al.   NATURE REVIEWS DRUG DISCOVERY

Dimerization Induced by C-Terminal 14–3–3 Binding Is Sufficient for BRAF Kinase Activation

(2020) Nicholas P.D. Liau et al.   BIOCHEMISTRY

Structural basis for the action of the drug trametinib at KSR-bound MEK

(2020) Zaigham M. Khan et al.   NATURE

Targeting Alterations in the RAF–MEK Pathway

(2019) Rona Yaeger et al.   Cancer Discovery

Architecture of autoinhibited and active BRAF–MEK1–14-3-3 complexes

(2019) Eunyoung Park et al.   NATURE

MEK drives BRAF activation through allosteric control of KSR proteins

(2018) Hugo Lavoie et al.   NATURE

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

(2018) Jimin Yuan et al.   ONCOGENE

SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signalling

(2018) Thomas Strub et al.   Nature Communications

CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles

(2017) P Jain et al.   ONCOGENE

Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling

(2016) Neil S. Dhawan et al.   NATURE

BRAF Mutants Evade ERK-Dependent Feedback by Different Mechanisms that Determine Their Sensitivity to Pharmacologic Inhibition

(2015) Zhan Yao et al.   CANCER CELL

Tunable-Combinatorial Mechanisms of Acquired Resistance Limit the Efficacy of BRAF/MEK Cotargeting but Result in Melanoma Drug Addiction

(2015) Gatien Moriceau et al.   CANCER CELL

Regulation of RAF protein kinases in ERK signalling

(2015) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Target engagement and drug residence time can be observed in living cells with BRET

(2015) Matthew B. Robers et al.   Nature Communications

Identification and Characterization of a Novel Chemotype MEK Inhibitor Able to Alter the Phosphorylation State of MEK1/2

(2015) Takayuki Yoshida et al.   Oncotarget

Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling

(2014) Jacob R. Haling et al.   CANCER CELL

Disruption of CRAF-Mediated MEK Activation Is Required for Effective MEK Inhibition in KRAS Mutant Tumors

(2014) Piro Lito et al.   CANCER CELL

Targeting RAS–ERK signalling in cancer: promises and challenges

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

Crystal structure of a BRAF kinase domain monomer explains basis for allosteric regulation

(2014) Neroshan Thevakumaran et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma

(2014) Georgina V. Long et al.   Nature Communications

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

(2013) Georgia Hatzivassiliou et al.   NATURE

Tumor adaptation and resistance to RAF inhibitors

(2013) Piro Lito et al.   NATURE MEDICINE

MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

(2013) N. Wagle et al.   Cancer Discovery

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

(2011) Poulikos I. Poulikakos et al.   NATURE

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

A dimerization-dependent mechanism drives RAF catalytic activation

(2009) Thanashan Rajakulendran et al.   NATURE