Approaches of targeting Rho GTPases in cancer drug discovery

Rho Kinase Inhibitors Block Melanoma Cell Migration and Inhibit Metastasis

(2015) Amine Sadok et al.   CANCER RESEARCH

Rho family GTPases: Making it to the third dimension

(2015) Kristin M. Riching et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

The RHOA G17V gene mutation occurs frequently in peripheral T-cell lymphoma and is associated with a characteristic molecular signature

(2014) R. Manso et al.   BLOOD

CDC42 Inhibition Suppresses Progression of Incipient Intestinal Tumors

(2014) R. Sakamori et al.   CANCER RESEARCH

The RAC1 P29S Hotspot Mutation in Melanoma Confers Resistance to Pharmacological Inhibition of RAF

(2014) Ian R. Watson et al.   CANCER RESEARCH

A novel small-molecule MRCK inhibitor blocks cancer cell invasion

(2014) Mathieu Unbekandt et al.   Cell Communication and Signaling

Mutational Landscape of Aggressive Cutaneous Squamous Cell Carcinoma

(2014) C. R. Pickering et al.   CLINICAL CANCER RESEARCH

RecurrentRHOAmutations in pediatric Burkitt lymphoma treated according to the NHL-BFM protocols

(2014) Marius Rohde et al.   GENES CHROMOSOMES & CANCER

Inhibitors of p21-Activated Kinases (PAKs)

(2014) Joachim Rudolph et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma

(2014) Miwako Kakiuchi et al.   NATURE GENETICS

A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma

(2014) Hae Yong Yoo et al.   NATURE GENETICS

RPEL Proteins Are the Molecular Targets for CCG-1423, an Inhibitor of Rho Signaling

(2014) Ken’ichiro Hayashi et al.   PLoS One

Phase 2 Randomized Clinical Study of a Rho Kinase Inhibitor, K-115, in Primary Open-Angle Glaucoma and Ocular Hypertension

(2013) Hidenobu Tanihara et al.   AMERICAN JOURNAL OF OPHTHALMOLOGY

In vitro and in vivo effects of geranylgeranyltransferase I inhibitor P61A6 on non-small cell lung cancer cells

(2013) Drazen B Zimonjic et al.   BMC CANCER

Dimensions in cell migration

(2013) Andrew D Doyle et al.   CURRENT OPINION IN CELL BIOLOGY

Advances in the studies of roles of Rho/Rho-kinase in diseases and the development of its inhibitors

(2013) Ronggui Guan et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

FRAX597, a Small Molecule Inhibitor of the p21-activated Kinases, Inhibits Tumorigenesis of Neurofibromatosis Type 2 (NF2)-associated Schwannomas

(2013) Silvia Licciulli et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cell Type-specific Signaling Function of RhoA GTPase: Lessons from Mouse Gene Targeting

(2013) Xuan Zhou et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Characterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe

(2013) Lin Hong et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

P21-Activated Kinase 1 (PAK1) as a Therapeutic Target in BRAF Wild-Type Melanoma

(2013) Christy C. Ong et al.   JNCI-Journal of the National Cancer Institute

Targeting Cdc42 with the small molecule drug AZA197 suppresses primary colon cancer growth and prolongs survival in a preclinical mouse xenograft model by downregulation of PAK1 activity

(2013) Karin Zins et al.   Journal of Translational Medicine

Drug for an 'undruggable' protein

(2013) Nicole M. Baker et al.   NATURE

Identification of novel ROCK inhibitors with anti-migratory and anti-invasive activities

(2013) R A Patel et al.   ONCOGENE

Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in development and disease

(2013) D R Cook et al.   ONCOGENE

A Rac1/Cdc42 GTPase-Specific Small Molecule Inhibitor Suppresses Growth of Primary Human Prostate Cancer Xenografts and Prolongs Survival in Mice

(2013) Karin Zins et al.   PLoS One

Targeted genetic dependency screen facilitates identification of actionable mutations in FGFR4, MAP3K9, and PAK5 in lung cancer

(2013) S. Fawdar et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Small-molecule inhibitors targeting G-protein-coupled Rho guanine nucleotide exchange factors

(2013) X. Shang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Small molecule targeting Cdc42–intersectin interaction disrupts Golgi organization and suppresses cell motility

(2013) Amy Friesland et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

RAC1P29S is a spontaneously activating cancer-associated GTPase

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

Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro

(2012) Henry I C Lowe et al.   Cancer Cell International

RKI-1447 Is a Potent Inhibitor of the Rho-Associated ROCK Kinases with Anti-Invasive and Antitumor Activities in Breast Cancer

(2012) R. A. Patel et al.   CANCER RESEARCH

Identification of somatic mutations in non-small cell lung carcinomas using whole-exome sequencing

(2012) Pengyuan Liu et al.   CARCINOGENESIS

A Landscape of Driver Mutations in Melanoma

(2012) Eran Hodis et al.   CELL

Cdc42 Activity Regulates Hematopoietic Stem Cell Aging and Rejuvenation

(2012) Maria Carolina Florian et al.   Cell Stem Cell

Rational Design of Small Molecule Inhibitors Targeting RhoA Subfamily Rho GTPases

(2012) Xun Shang et al.   CHEMISTRY & BIOLOGY

Rational Design of Small Molecule Inhibitors Targeting the Rac GTPase-p67phox Signaling Axis in Inflammation

(2012) Emily E. Bosco et al.   CHEMISTRY & BIOLOGY

AT13148 Is a Novel, Oral Multi-AGC Kinase Inhibitor with Potent Pharmacodynamic and Antitumor Activity

(2012) T. A. Yap et al.   CLINICAL CANCER RESEARCH

Is there a future for prenyltransferase inhibitors in cancer therapy?

(2012) Sarah A Holstein et al.   CURRENT OPINION IN PHARMACOLOGY

Rho-associated kinases in tumorigenesis: re-considering ROCK inhibition for cancer therapy

(2012) Nicola Rath et al.   EMBO REPORTS

Characterization of EHop-016, Novel Small Molecule Inhibitor of Rac GTPase

(2012) Brenda L. Montalvo-Ortiz et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fragment-Based and Structure-Guided Discovery and Optimization of Rho Kinase Inhibitors

(2012) Rongshi Li et al.   JOURNAL OF MEDICINAL CHEMISTRY

Knockdown of PAK4 or PAK1 Inhibits the Proliferation of Mutant KRAS Colon Cancer Cells Independently of RAF/MEK/ERK and PI3K/AKT Signaling

(2012) H. Tabusa et al.   MOLECULAR CANCER RESEARCH

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

(2012) Michael Krauthammer et al.   NATURE GENETICS

PAK4 kinase activity and somatic mutation promote carcinoma cell motility and influence inhibitor sensitivity

(2012) A D Whale et al.   ONCOGENE

Essential Role of Cdc42 in Ras-Induced Transformation Revealed by Gene Targeting

(2012) Kristy R. Stengel et al.   PLoS One

Ocular Hypotensive Effect of the Rho Kinase Inhibitor AR-12286 in Patients With Glaucoma and Ocular Hypertension

(2011) Robert D. Williams et al.   AMERICAN JOURNAL OF OPHTHALMOLOGY

LCH-7749944, a novel and potent p21-activated kinase 4 inhibitor, suppresses proliferation and invasion in human gastric cancer cells

(2011) Jian Zhang et al.   CANCER LETTERS

Clinical Validation of Colorectal Cancer Biomarkers Identified from Bioinformatics Analysis of Public Expression Data

(2011) Y. Jung et al.   CLINICAL CANCER RESEARCH

Chelerythrine perturbs lamellar actomyosin filaments by selective inhibition of myotonic dystrophy kinase-related Cdc42-binding kinase

(2011) Ivan Tan et al.   FEBS LETTERS

Methylation status of T-lymphoma invasion and metastasis 1 promoter and its overexpression in colorectal cancer

(2011) He Jin et al.   HUMAN PATHOLOGY

Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration

(2011) Violaine D. Delorme-Walker et al.   JOURNAL OF CELL BIOLOGY

Deep sequencing of gastric carcinoma reveals somatic mutations relevant to personalized medicine

(2011) Joanna D Holbrook et al.   Journal of Translational Medicine

The 'invisible hand': regulation of RHO GTPases by RHOGDIs

(2011) Rafael Garcia-Mata et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling

(2011) Y Shrestha et al.   ONCOGENE

Identification and Characterization of Mechanism of Action of P61-E7, a Novel Phosphine Catalysis-Based Inhibitor of Geranylgeranyltransferase-I

(2011) Lai N. Chan et al.   PLoS One

Targeting p21-activated kinase 1 (PAK1) to induce apoptosis of tumor cells

(2011) C. C. Ong et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

The Mutational Landscape of Head and Neck Squamous Cell Carcinoma

(2011) N. Stransky et al.   SCIENCE

Signaling mechanisms of inhibition of phospholipase D activation by CHS-111 in formyl peptide-stimulated neutrophils

(2010) Ling-Chu Chang et al.   BIOCHEMICAL PHARMACOLOGY

Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers

(2010) Mei Wu et al.   CANCER

Copy number alterations in pancreatic cancer identify recurrentPAK4amplification

(2010) Shuaili Chen et al.   CANCER BIOLOGY & THERAPY

Guanine nucleotide exchange factors for RhoGTPases: Good therapeutic targets for cancer therapy?

(2010) Galit Lazer et al.   CELLULAR SIGNALLING

RhoGDI signaling provides targets for cancer therapy

(2010) Michael A. Harding et al.   EUROPEAN JOURNAL OF CANCER

Signaling Role of Cdc42 in Regulating Mammalian Physiology

(2010) Jaime Melendez et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

p120-catenin is a binding partner and substrate for Group B Pak kinases

(2010) Lisa Epstein Wong et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Tetrahydroisoquinoline Derivatives As Highly Selective and Potent Rho Kinase Inhibitors

(2010) Xingang Fang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of the Rac-GEF P-Rex1 as an Essential Mediator of ErbB Signaling in Breast Cancer

(2010) Maria Soledad Sosa et al.   MOLECULAR CELL

Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA

(2010) Jie Ding et al.   NATURE CELL BIOLOGY

Small molecules discovered in a pathway screen target the Rho pathway in cytokinesis

(2010) Adam B Castoreno et al.   Nature Chemical Biology

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

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

Rac1 is crucial for Ras-dependent skin tumor formation by controlling Pak1-Mek-Erk hyperactivation and hyperproliferation in vivo

(2010) Z Wang et al.   ONCOGENE

NF2-deficient cells depend on the Rac1-canonical Wnt signaling pathway to promote the loss of contact inhibition of proliferation

(2010) E E Bosco et al.   ONCOGENE

Activating ROCK1 somatic mutations in human cancer

(2010) P A Lochhead et al.   ONCOGENE

Endothelial-Rac1 Is Not Required for Tumor Angiogenesis unless αvβ3-Integrin Is Absent

(2010) Gabriela D'Amico et al.   PLoS One

Small-molecule p21-activated kinase inhibitor PF-3758309 is a potent inhibitor of oncogenic signaling and tumor growth

(2010) B. W. Murray et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Rho GDP Dissociation Inhibitor 2 Suppresses Metastasis via Unconventional Regulation of RhoGTPases

(2009) K. Moissoglu et al.   CANCER RESEARCH

Identification ofPAK4as a putative target gene for amplification within 19q13.12-q13.2 in oral squamous-cell carcinoma

(2009) Asma Begum et al.   CANCER SCIENCE

PAK kinase regulates Rac GTPase and is a potential target in human schwannomas

(2009) Christine Flaiz et al.   EXPERIMENTAL NEUROLOGY

Pharmacological Characterization of SAR407899, a Novel Rho-Kinase Inhibitor

(2009) Matthias Löhn et al.   HYPERTENSION

Abnormal expression of p120-catenin, E-cadherin, and small GTPases is significantly associated with malignant phenotype of human lung cancer

(2009) Yang Liu et al.   LUNG CANCER

Consensus transcriptome signature of perineural invasion in pancreatic carcinoma

(2009) I. Abiatari et al.   MOLECULAR CANCER THERAPEUTICS

In vivo antitumor effect of a novel inhibitor of protein geranylgeranyltransferase-I

(2009) J. Lu et al.   MOLECULAR CANCER THERAPEUTICS

An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently

(2009) J. Viaud et al.   MOLECULAR CANCER THERAPEUTICS

Ect2 links the PKCι–Par6α complex to Rac1 activation and cellular transformation

(2009) V Justilien et al.   ONCOGENE

Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis

(2009) J Qin et al.   ONCOGENE

Activation of Rho GTPases by DOCK Exchange Factors Is Mediated by a Nucleotide Sensor

(2009) J. Yang et al.   SCIENCE

Activation of the PI3K Pathway in Cancer Through Inhibition of PTEN by Exchange Factor P-REX2a

(2009) B. Fine et al.   SCIENCE

The Guanine Nucleotide Exchange Factors Trio, Ect2, and Vav3 Mediate the Invasive Behavior of Glioblastoma

(2008) Bodour Salhia et al.   AMERICAN JOURNAL OF PATHOLOGY

Intraocular Pressure–Lowering Effects and Safety of Topical Administration of a Selective ROCK Inhibitor, SNJ-1656, in Healthy Volunteers

(2008) Hidenobu Tanihara   ARCHIVES OF OPHTHALMOLOGY

7-Chloro-6-piperidin-1-yl-quinoline-5,8-dione (PT-262), a novel synthetic compound induces lung carcinoma cell death associated with inhibiting ERK and CDC2 phosphorylation via a p53-independent pathway

(2008) Tzu-Sheng Hsu et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A novel amplification target, ARHGAP5, promotes cell spreading and migration by negatively regulating RhoA in Huh-7 hepatocellular carcinoma cells

(2008) Yasuyuki Gen et al.   CANCER LETTERS

The Anaplastic Lymphoma Kinase Controls Cell Shape and Growth of Anaplastic Large Cell Lymphoma through Cdc42 Activation

(2008) Chiara Ambrogio et al.   CANCER RESEARCH

An Isoform-Selective, Small-Molecule Inhibitor Targets the Autoregulatory Mechanism of p21-Activated Kinase

(2008) Sean W. Deacon et al.   CHEMISTRY & BIOLOGY

Rho GTPases in PC-3 prostate cancer cell morphology, invasion and tumor cell diapedesis

(2008) Linda Sequeira et al.   CLINICAL & EXPERIMENTAL METASTASIS

The actin cytoskeleton in cancer cell motility

(2008) Michael F. Olson et al.   CLINICAL & EXPERIMENTAL METASTASIS

Involvement of Epithelial Cell Transforming Sequence-2 Oncoantigen in Lung and Esophageal Cancer Progression

(2008) D. Hirata et al.   CLINICAL CANCER RESEARCH

Epigenetic Inhibition of Nuclear Receptor Small Heterodimer Partner Is Associated With and Regulates Hepatocellular Carcinoma Growth

(2008) Nan He et al.   GASTROENTEROLOGY

Amplification of 11q13 in ovarian carcinoma

(2008) Lindsay A. Brown et al.   GENES CHROMOSOMES & CANCER

Inhibitors of Protein Geranylgeranyltransferase I and Rab Geranylgeranyltransferase Identified from a Library of Allenoate-derived Compounds

(2008) Masaru Watanabe et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Substituted 4-(Pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as Potent and Highly Selective Rho Kinase (ROCK-II) Inhibitors

(2008) Yangbo Feng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mixed-Lineage Kinase 1 and Mixed-Lineage Kinase 3 Subtype-Selective Dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: Optimization, Mixed-Lineage Kinase 1 Crystallography, and Oral in Vivo Activity in 1-Methyl-4-phenyltetrahydropyridine Models

(2008) Robert L. Hudkins et al.   JOURNAL OF MEDICINAL CHEMISTRY

Overexpression of Rho GDP-Dissociation Inhibitor Alpha Is Associated with Tumor Progression and Poor Prognosis of Colorectal Cancer

(2008) Liang Zhao et al.   JOURNAL OF PROTEOME RESEARCH

Targeting Large Kinase Active Site with Rigid, Bulky Octahedral Ruthenium Complexes

(2008) Jasna Maksimoska et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses

(2008) S. Jones et al.   SCIENCE

Cardiovascular effects of a novel potent and highly selective azaindole-based inhibitor of Rho-kinase

(2007) R Kast et al.   BRITISH JOURNAL OF PHARMACOLOGY