Druggable cancer phosphatases

The Rise of Molecular Glues

(2021) Stuart L. Schreiber   CELL

Phosphoproteome and drug response effects mediated by the three Protein Phosphatase 2A inhibitor proteins CIP2A, SET and PME-1

(2020) Otto Kauko et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells

(2020) Jong Wook Kim et al.   eLife

Molecular mechanism of SHP2 activation by PD-1 stimulation

(2020) M. Marasco et al.   Science Advances

Allosteric inhibition of SHP2 stimulates anti-tumor immunity by transforming the immunosuppressive environment

(2020) Elsa Quintana et al.   CANCER RESEARCH

Allosteric Activators of Protein Phosphatase 2A Display Broad Antitumor Activity Mediated by Dephosphorylation of MYBL2

(2020) Ken Morita et al.   CELL

Piecing Together a Broken Tumor Suppressor Phosphatase for Cancer Therapy

(2020) Jukka Westermarck et al.   CELL

Selective PP2A Enhancement through Biased Heterotrimer Stabilization

(2020) Daniel Leonard et al.   CELL

Mechanisms of site‐specific dephosphorylation and kinase opposition imposed by PP2A regulatory subunits

(2020) Thomas Kruse et al.   EMBO JOURNAL

Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

(2020) Mingliang Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective Inhibition of STRN3-Containing PP2A Phosphatase Restores Hippo Tumor-Suppressor Activity in Gastric Cancer

(2020) Yang Tang et al.   CANCER CELL

Good Guy in Bad Company: How STRNs Convert PP2A into an Oncoprotein

(2020) Kari J. Kurppa et al.   CANCER CELL

PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis

(2020) E. G. Garcia et al.   LEUKEMIA

Signalling input from divergent pathways subverts B cell transformation

(2020) Lai N. Chan et al.   NATURE

Mechanism of PRL2 phosphatase-mediated PTEN degradation and tumorigenesis

(2020) Qinglin Li et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation

(2020) Guangya Zhu et al.   CELL

Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation

(2019) Yoshihito Kano et al.   Nature Communications

The Antitumor Drug LB-100 Is a Catalytic Inhibitor of Protein Phosphatase 2A (PPP2CA) and 5 (PPP5C) Coordinating with the Active-Site Catalytic Metals in PPP5C

(2019) Brandon M. D'Arcy et al.   MOLECULAR CANCER THERAPEUTICS

The NMR-based characterization of the FTY720-SET complex reveals an alternative mechanism for the attenuation of the inhibitory SET-PP2A interaction

(2019) Ryan M. De Palma et al.   FASEB JOURNAL

Reactivation of PTEN tumor suppressor for cancer treatment through inhibition of a MYC-WWP1 inhibitory pathway

(2019) Yu-Ru Lee et al.   SCIENCE

The Phosphatase PRL-3 Is Involved in Key Steps of Cancer Metastasis

(2019) Laura Duciel et al.   JOURNAL OF MOLECULAR BIOLOGY

Targeting PDGFRα-activated Glioblastoma through Specific Inhibition of SHP-2-mediated Signaling

(2019) Youzhou Sang et al.   NEURO-ONCOLOGY

PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein

(2019) Min Thura et al.   Nature Communications

Tumor intrinsic efficacy by SHP2 and RTK inhibitors in KRAS mutant cancers

(2019) Huai-Xiang Hao et al.   MOLECULAR CANCER THERAPEUTICS

Vertical pathway inhibition overcomes adaptive feedback resistance to KRASG12C inhibition

(2019) Meagan B. Ryan et al.   CLINICAL CANCER RESEARCH

Deregulating MYC in a model of HER2+ breast cancer mimics human intertumoral heterogeneity

(2019) Tyler Risom et al.   JOURNAL OF CLINICAL INVESTIGATION

Next-Generation Cell-Active Inhibitors of the Undrugged Oncogenic PTP4A3 Phosphatase

(2019) John S. Lazo et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity

(2019) Carmen Vicente et al.   CANCER LETTERS

Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers

(2019) Caroline C. Farrington et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Dual Allosteric Inhibition of SHP2 Phosphatase

(2018) Michelle Fodor et al.   ACS Chemical Biology

Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistance

(2018) Qi-Nian Wu et al.   CANCER LETTERS

Tumor suppressive protein phosphatases in human cancer: Emerging targets for therapeutic intervention and tumor stratification

(2018) Bob Meeusen et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Stepping out of the shadows: Oncogenic and tumor-promoting protein tyrosine phosphatases

(2018) Ari Elson   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

A fine balancing act: A delicate kinase-phosphatase equilibrium that protects against chromosomal instability and cancer

(2018) Marilia Henriques Cordeiro et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Non-genomic mechanisms of protein phosphatase 2A (PP2A) regulation in cancer

(2018) Otto Kauko et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase

(2018) Dietrich A. Ruess et al.   NATURE MEDICINE

Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition

(2018) Gabrielle S. Wong et al.   NATURE MEDICINE

SHP2 inhibition restores sensitivity in ALK-rearranged non-small-cell lung cancer resistant to ALK inhibitors

(2018) Leila Dardaei et al.   NATURE MEDICINE

The functions and regulation of the PTEN tumour suppressor: new modes and prospects

(2018) Yu-Ru Lee et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells

(2018) Otto Kauko et al.   Science Translational Medicine

Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined with PD-1 blockade

(2018) Winson S. Ho et al.   Nature Communications

Targeted therapies don't work for a reason; the neglected tumor suppressor phosphatase PP2A strikes back

(2018) Jukka Westermarck   FEBS Journal

SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models

(2018) Carmine Fedele et al.   Cancer Discovery

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade

(2018) Mingxia Zhao et al.   Acta Pharmaceutica Sinica B

Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL

(2018) Mario Angelo Pagano et al.   LEUKEMIA

Mechanism of activating mutations and allosteric drug inhibition of the phosphatase SHP2

(2018) Ricardo A. P. Pádua et al.   Nature Communications

Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition

(2018) Jonathan R. LaRochelle et al.   Nature Communications

The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

(2017) Fatima Ardito et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

A potent, selective, and orally bioavailable inhibitor of the protein-tyrosine phosphatase PTP1B improves insulin and leptin signaling in animal models

(2017) Navasona Krishnan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

(2017) Jaya Sangodkar et al.   JOURNAL OF CLINICAL INVESTIGATION

A Tumor Cell-Selective Inhibitor of Mitogen-Activated Protein Kinase Phosphatases Sensitizes Breast Cancer Cells to Lymphokine-Activated Killer Cell Activity

(2017) Christof T. Kaltenmeier et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration

(2017) Ariadna Tibau et al.   JNCI-Journal of the National Cancer Institute

Targeting c-FOS and DUSP1 abrogates intrinsic resistance to tyrosine-kinase inhibitor therapy in BCR-ABL-induced leukemia

(2017) Meenu Kesarwani et al.   NATURE MEDICINE

The target landscape of clinical kinase drugs

(2017) Susan Klaeger et al.   SCIENCE

Targeting ovarian cancer and endothelium with an allosteric PTP4A3 phosphatase inhibitor

(2017) Kelley E. McQueeney et al.   Oncotarget

Magnitude of Clinical Benefit of Cancer Drugs Approved by the US Food and Drug Administration

(2017) Ariadna Tibau et al.   JNCI-Journal of the National Cancer Institute

Regulation of protein phosphatase 2A (PP2A) tumor suppressor function by PME-1

(2016) A. Kaur et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

PP2A Inhibitor PME-1 Drives Kinase Inhibitor Resistance in Glioma Cells

(2016) Amanpreet Kaur et al.   CANCER RESEARCH

Molecular Pathways: Maintaining MAPK Inhibitor Sensitivity by Targeting Nonmutational Tolerance

(2016) M. P. Smith et al.   CLINICAL CANCER RESEARCH

Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth

(2016) Elie Kostantin et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

(2016) Ying-Nan P. Chen et al.   NATURE

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

(2016) Shaokun Shu et al.   NATURE

PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia

(2016) Robert S. Banh et al.   NATURE CELL BIOLOGY

Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor

(2016) Joseph M. Salamoun et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs)

(2016) Andrew M. Kidger et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Role of DUSP1/MKP1 in tumorigenesis, tumor progression and therapy

(2016) Jiliang Shen et al.   Cancer Medicine

Reengineered tricyclic anti-cancer agents

(2015) David B. Kastrinsky et al.   BIOORGANIC & MEDICINAL CHEMISTRY

LB100, a small molecule inhibitor of PP2A with potent chemo- and radio-sensitizing potential

(2015) Christopher S Hong et al.   CANCER BIOLOGY & THERAPY

Erk Negative Feedback Control Enables Pre-B Cell Transformation and Represents a Therapeutic Target in Acute Lymphoblastic Leukemia

(2015) Seyedmehdi Shojaee et al.   CANCER CELL

Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis

(2015) Severa Bunda et al.   Nature Communications

From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies

(2015) Maria Ciccone et al.   Frontiers in Oncology

In Vivo Structure-Activity Relationship Studies Support Allosteric Targeting of a Dual Specificity Phosphatase

(2014) Vasiliy N. Korotchenko et al.   CHEMBIOCHEM

Antagonism of SET Using OP449 Enhances the Efficacy of Tyrosine Kinase Inhibitors and Overcomes Drug Resistance in Myeloid Leukemia

(2014) A. Agarwal et al.   CLINICAL CANCER RESEARCH

Membrane protein CNNM4–dependent Mg2+ efflux suppresses tumor progression

(2014) Yosuke Funato et al.   JOURNAL OF CLINICAL INVESTIGATION

Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia

(2014) Alejandro Gutierrez et al.   JOURNAL OF CLINICAL INVESTIGATION

The Antiproliferative Response of Indole-3-Carbinol in Human Melanoma Cells Is Triggered by an Interaction with NEDD4-1 and Disruption of Wild-Type PTEN Degradation

(2014) Ida Aronchik et al.   MOLECULAR CANCER RESEARCH

Targeting the disordered C terminus of PTP1B with an allosteric inhibitor

(2014) Navasona Krishnan et al.   Nature Chemical Biology

Ultradeep Human Phosphoproteome Reveals a Distinct Regulatory Nature of Tyr and Ser/Thr-Based Signaling

(2014) Kirti Sharma et al.   Cell Reports

PP2A-activating drugs selectively eradicate TKI-resistant chronic myeloid leukemic stem cells

(2013) Paolo Neviani et al.   JOURNAL OF CLINICAL INVESTIGATION

Identification of Cryptotanshinone as an Inhibitor of Oncogenic Protein Tyrosine Phosphatase SHP2 (PTPN11)

(2013) Wei Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Senescence Sensitivity of Breast Cancer Cells Is Defined by Positive Feedback Loop between CIP2A and E2F1

(2013) Anni Laine et al.   Cancer Discovery

Molecular Pathways: Targeting Mdm2 and Mdm4 in Cancer Therapy

(2012) Q. Li et al.   CLINICAL CANCER RESEARCH

Sphingosine analogue drug FTY720 targets I2PP2A/SET and mediates lung tumour suppression via activation of PP2A-RIPK1-dependent necroptosis

(2012) Sahar A. Saddoughi et al.   EMBO Molecular Medicine

CIP2A Promotes Proliferation of Spermatogonial Progenitor Cells and Spermatogenesis in Mice

(2012) Sami Ventelä et al.   PLoS One

Pharmacodynamic Effects of Steady-State Fingolimod on Antibody Response in Healthy Volunteers: A 4-Week, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Dose Study

(2011) Craig Boulton et al.   JOURNAL OF CLINICAL PHARMACOLOGY

A large-scale method to measure absolute protein phosphorylation stoichiometries

(2011) Ronghu Wu et al.   NATURE METHODS

Salicylic Acid Based Small Molecule Inhibitor for the Oncogenic Src Homology-2 Domain Containing Protein Tyrosine Phosphatase-2 (SHP2)

(2010) Xian Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

DUSP1/MKP1 promotes angiogenesis, invasion and metastasis in non-small-cell lung cancer

(2010) V Moncho-Amor et al.   ONCOGENE

The Substrate of Greatwall Kinase, Arpp19, Controls Mitosis by Inhibiting Protein Phosphatase 2A

(2010) A. Gharbi-Ayachi et al.   SCIENCE

PME-1 Protects Extracellular Signal-Regulated Kinase Pathway Activity from Protein Phosphatase 2A-Mediated Inactivation in Human Malignant Glioma

(2009) P. Puustinen et al.   CANCER RESEARCH

Serine/Threonine Phosphatases: Mechanism through Structure

(2009) Yigong Shi   CELL

From Promiscuity to Precision: Protein Phosphatases Get a Makeover

(2009) David M. Virshup et al.   MOLECULAR CELL

Zebrafish chemical screening reveals an inhibitor of Dusp6 that expands cardiac cell lineages

(2009) Gabriela Molina et al.   Nature Chemical Biology

Multiple pathways regulated by the tumor suppressor PP2A in transformation

(2008) Jukka Westermarck et al.   TRENDS IN MOLECULAR MEDICINE