Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling

(2016) Sai Krishna Athuluri-Divakar et al.   CELL

Loss of wild-type Kras promotes activation of all Ras isoforms in oncogenic Kras-induced leukemogenesis

(2016) G Kong et al.   LEUKEMIA

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

(2016) P. Lito et al.   SCIENCE

Identification of pyrazolopyridazinones as PDEδ inhibitors

(2016) Björn Papke et al.   Nature Communications

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling

(2015) Man-Tzu Wang et al.   CELL

Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation

(2015) Jon J. G. Winter et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biochemical and Structural Analysis of Common Cancer-Associated KRAS Mutations

(2015) J. C. Hunter et al.   MOLECULAR CANCER RESEARCH

Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices

(2015) Elizaveta S. Leshchiner et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway

(2015) Xiaolin Nan et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif

(2015) Frederick D. Tsai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

GTP-Dependent K-Ras Dimerization

(2015) Serena Muratcioglu et al.   STRUCTURE

Dragging Ras Back in the Ring

(2014) Andrew G. Stephen et al.   CANCER CELL

Wild-type KRAS inhibits oncogenic KRAS-induced T-ALL in mice

(2014) A Staffas et al.   LEUKEMIA

H-Ras forms dimers on membrane surfaces via a protein-protein interface

(2014) W.-C. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange

(2014) Michael C. Burns et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Therapeutic Targeting of Oncogenic K-Ras by a Covalent Catalytic Site Inhibitor

(2013) Sang Min Lim et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A requirement for wild-type Ras isoforms in mutant KRas-driven signalling and transformation

(2013) Carolyn Bentley et al.   BIOCHEMICAL JOURNAL

Defective K-Ras oncoproteins overcome impaired effector activation to initiate leukemia in vivo

(2013) A. Shieh et al.   BLOOD

Requirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance

(2013) Esther Castellano et al.   CANCER CELL

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

(2013) Jonathan M. Ostrem et al.   NATURE

Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

(2013) Gunther Zimmermann et al.   NATURE

Targeting BTK with Ibrutinib in Relapsed or Refractory Mantle-Cell Lymphoma

(2013) Michael L. Wang et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting BTK with Ibrutinib in Relapsed Chronic Lymphocytic Leukemia

(2013) John C. Byrd et al.   NEW ENGLAND JOURNAL OF MEDICINE

Oncogenic K-Ras requires activation for enhanced activity

(2013) H Huang et al.   ONCOGENE

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

(2013) H. J. Hocker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

In silico discovery of small-molecule Ras inhibitors that display antitumor activity by blocking the Ras-effector interaction

(2013) F. Shima et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NMR-based functional profiling of RASopathies and oncogenic RAS mutations

(2013) M. J. Smith et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Stabilizing the Pro-Apoptotic BimBH3 Helix (BimSAHB) Does Not Necessarily Enhance Affinity or Biological Activity

(2012) Toru Okamoto et al.   ACS Chemical Biology

EGF Receptor Signaling Is Essential for K-Ras Oncogene-Driven Pancreatic Ductal Adenocarcinoma

(2012) Carolina Navas et al.   CANCER CELL

EGF Receptor Is Required for KRAS-Induced Pancreatic Tumorigenesis

(2012) Christine M. Ardito et al.   CANCER CELL

A Comprehensive Survey of Ras Mutations in Cancer

(2012) I. A. Prior et al.   CANCER RESEARCH

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

(2012) T. Maurer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Solution Structure of the State 1 Conformer of GTP-bound H-Ras Protein and Distinct Dynamic Properties between the State 1 and State 2 Conformers

(2011) Mitsugu Araki et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Mutant K-Ras Activation of the Proapoptotic MST2 Pathway Is Antagonized by Wild-Type K-Ras

(2011) David Matallanas et al.   MOLECULAR CELL

A Raf-induced allosteric transition of KSR stimulates phosphorylation of MEK

(2011) Damian F. Brennan et al.   NATURE

An orthosteric inhibitor of the Ras-Sos interaction

(2011) Anupam Patgiri et al.   Nature Chemical Biology

Molecular predictors of outcome in a phase 3 study of gemcitabine and erlotinib therapy in patients with advanced pancreatic cancer

(2010) Gilda da Cunha Santos et al.   CANCER

Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival

(2010) Matthias Drosten et al.   EMBO JOURNAL

Structural Basis for Conformational Dynamics of GTP-bound Ras Protein

(2010) Fumi Shima et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer

(2010) S. A. Forbes et al.   NUCLEIC ACIDS RESEARCH

Allosteric modulation of Ras positions Q61 for a direct role in catalysis

(2010) G. Buhrman et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural basis for the specific inhibition of heterotrimeric Gq protein by a small molecule

(2010) A. Nishimura et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer

(2010) M. Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Selective cytotoxicity of a bicyclic Ras inhibitor in cancer cells expressing K-RasG13D

(2009) Alessandro Palmioli et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Characterization of a Ras Mutant with Identical GDP- and GTP-Bound Structures,

(2009) Bradley Ford et al.   BIOCHEMISTRY

A dimerization-dependent mechanism drives RAF catalytic activation

(2009) Thanashan Rajakulendran et al.   NATURE

Non-steroidal anti-inflammatory drugs suppress the ERK signaling pathway via block of Ras/c-Raf interaction and activation of MAP kinase phosphatases

(2008) Mei-Ren Pan et al.   CELLULAR SIGNALLING

Farnesyltransferase Inhibitors: A Detailed Chemical View on an Elusive Biological Problem

(2008) Sergio Sousa et al.   CURRENT MEDICINAL CHEMISTRY

Wild-TypeKRASIs Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer

(2008) Rafael G. Amado et al.   JOURNAL OF CLINICAL ONCOLOGY

K-rasMutations and Benefit from Cetuximab in Advanced Colorectal Cancer

(2008) Christos S. Karapetis et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mapping the Nucleotide and Isoform-Dependent Structural and Dynamical Features of Ras Proteins

(2008) Alemayehu A. Gorfe et al.   STRUCTURE