Progress in developing MNK inhibitors

Stepwise Evolution of Fragment Hits against MAPK Interacting Kinases 1 and 2

(2020) Jacek Kwiatkowski et al.   JOURNAL OF MEDICINAL CHEMISTRY

MAPK-interacting kinase 2 (MNK2) regulates adipocyte metabolism independently of its catalytic activity

(2020) James E. Merrett et al.   BIOCHEMICAL JOURNAL

The cytokine storm and COVID‐19

(2020) Biying Hu et al.   JOURNAL OF MEDICAL VIROLOGY

Newcastle Disease virus infection activates PI3K/Akt/mTOR and p38 MAPK/Mnk1 pathways to benefit viral mRNA translation via interaction of the viral NP protein and host eIF4E

(2020) Yuan Zhan et al.   PLoS Pathogens

Disabling MNK protein kinases promotes oxidative metabolism and protects against diet-induced obesity

(2020) Lauren Y. Sandeman et al.   Molecular Metabolism

Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia

(2020) Liang-Chieh Chen et al.   JOURNAL OF NATURAL PRODUCTS

MNK1/NODAL signaling promotes invasive progression of breast ductal carcinoma in situ

(2019) Qianyu Guo et al.   CANCER RESEARCH

The MAP kinase-interacting kinases (MNKs) as targets in oncology

(2019) Jianling Xie et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Translation control of the immune checkpoint in cancer and its therapeutic targeting

(2019) Yichen Xu et al.   NATURE MEDICINE

The Novel Mnk1/2 Degrader and Apoptosis Inducer VNLG-152 Potently Inhibits TNBC Tumor Growth and Metastasis

(2019) Senthilmurugan Ramalingam et al.   Cancers

Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma

(2019) Min Zhang et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Synthesis and evaluation of 2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione derivatives as Mnk inhibitors

(2019) Ahmed M. Abdelaziz et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

First‐in‐Human, Healthy Volunteers Integrated Protocol of ETC‐206, an Oral Mnk 1/2 Kinase Inhibitor Oncology Drug

(2019) Vincenzo Teneggi et al.   CTS-Clinical and Translational Science

Targeting Tyrosine Kinases in Acute Myeloid Leukemia: Why, Who and How?

(2019) Solène Fernandez et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Eukaryotic initiation factor 4E (eIF4E): A recap of the cap‐binding protein

(2019) Asiya Batool et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Discovery of novel Mnk inhibitors using mutation‐based induced‐fit virtual high‐throughput screening

(2019) Rama K. Mishra et al.   Chemical Biology & Drug Design

Reversal of peripheral nerve injury-induced neuropathic pain and cognitive dysfunction via genetic and tomivosertib targeting of MNK

(2019) Stephanie Shiers et al.   NEUROPSYCHOPHARMACOLOGY

Galeterone and The Next Generation Galeterone Analogs, VNPP414 and VNPP433-3β Exert Potent Therapeutic Effects in Castration-/Drug-Resistant Prostate Cancer Preclinical Models In Vitro and In Vivo

(2019) Andrew K. Kwegyir-Afful et al.   Cancers

Deciphering the mechanistic effects of eIF4E phosphorylation on mRNA‐cap recognition

(2019) Dilraj Lama et al.   PROTEIN SCIENCE

Inhibitory effects of SEL201 in acute myeloid leukemia

(2019) Ewa M. Kosciuczuk et al.   Oncotarget

The retinamide VNLG-152 inhibits f-AR/AR-V7 and MNK-eIF4E signaling pathways to suppress EMT and castration-resistant prostate cancer xenograft growth

(2018) Vidya P. Ramamurthy et al.   FEBS Journal

Structure-based Design of Pyridone–Aminal eFT508 Targeting Dysregulated Translation by Selective Mitogen-activated Protein Kinase Interacting Kinases 1 and 2 (MNK1/2) Inhibition

(2018) Siegfried H. Reich et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Selective Mitogen-Activated Protein Kinase Interacting Kinases 1 and 2 Inhibitors for the Treatment of Blast Crisis Leukemia

(2018) Haiyan Yang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Loss of eIF4E phosphorylation engenders depression-like behaviors via selective mRNA translation

(2018) Inês Silva Amorim et al.   JOURNAL OF NEUROSCIENCE

Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils

(2018) Nathaniel Robichaud et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Role of MAPK/MNK1 signaling in virus replication

(2018) Ram Kumar et al.   VIRUS RESEARCH

Therapeutic Opportunities in Eukaryotic Translation

(2018) Jennifer Chu et al.   Cold Spring Harbor Perspectives in Biology

Translational control of depression-like behavior via phosphorylation of eukaryotic translation initiation factor 4E

(2018) Argel Aguilar-Valles et al.   Nature Communications

Synergistic effects of inhibiting the MNK-eIF4E and PI3K/AKT/ mTOR pathways on cell migration in MDA-MB-231 cells

(2018) Ella Lineham et al.   Oncotarget

Increased expression of MNK1b, the spliced isoform of MNK1, predicts poor prognosis and is associated with triple-negative breast cancer

(2018) Celia Pinto-Díez et al.   Oncotarget

A novel inhibitor stabilizes the inactive conformation of MAPK-interacting kinase 1

(2018) Yumi Matsui et al.   Acta Crystallographica Section F-Structural Biology Communications

eIF4E Phosphorylation in Prostate Cancer

(2018) Leandro S. D'Abronzo et al.   NEOPLASIA

Probing the Anticancer Action of Novel Ferrocene Analogues of MNK Inhibitors

(2018) Supojjanee Sansook et al.   MOLECULES

MNK1 inhibitor CGP57380 overcomes mTOR inhibitor-induced activation of eIF4E: the mechanism of synergic killing of human T-ALL cells

(2018) Xian-bo Huang et al.   ACTA PHARMACOLOGICA SINICA

MNK1 inhibitor as an antiviral agent suppresses buffalopox virus protein synthesis

(2018) Ram Kumar et al.   ANTIVIRAL RESEARCH

Design, synthesis and activity of Mnk1 and Mnk2 selective inhibitors containing thieno[2,3-d]pyrimidine scaffold

(2018) Xin Jin et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Hyperactive mTOR and MNK1 phosphorylation of eIF4E confer tamoxifen resistance and estrogen independence through selective mRNA translation reprogramming

(2017) Phillip A. Geter et al.   GENES & DEVELOPMENT

MNK1/2 inhibition limits oncogenicity and metastasis of KIT-mutant melanoma

(2017) Yao Zhan et al.   JOURNAL OF CLINICAL INVESTIGATION

The MNK–eIF4E Signaling Axis Contributes to Injury-Induced Nociceptive Plasticity and the Development of Chronic Pain

(2017) Jamie K. Moy et al.   JOURNAL OF NEUROSCIENCE

Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is Regulated by MNK1 and mRNA Translation

(2017) Jonathan B. Bell et al.   MOLECULAR CANCER RESEARCH

The androgen receptor is a negative regulator of eIF4E phosphorylation at S209: implications for the use of mTOR inhibitors in advanced prostate cancer

(2017) L S D'Abronzo et al.   ONCOGENE

Brd4 modulates the innate immune response through Mnk2–eIF4E pathway-dependent translational control of IκBα

(2017) Yan Bao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Suppression Of β-catenin Nuclear Translocation By CGP57380 Decelerates Poor Progression And Potentiates Radiation-Induced Apoptosis in Nasopharyngeal Carcinoma

(2017) Weiyuan Wang et al.   Theranostics

MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1

(2017) Michael C. Brown et al.   Cell Reports

MAP kinase-interacting serine/threonine kinase 2 promotes proliferation, metastasis, and predicts poor prognosis in non-small cell lung cancer

(2017) Zhihua Guo et al.   Scientific Reports

Anthelmintic drug niclosamide enhances the sensitivity of chronic myeloid leukemia cells to dasatinib through inhibiting Erk/Mnk1/eIF4E pathway

(2016) Zhong Liu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Inhibition of eukaryotic initiation factor 4E phosphorylation by cercosporamide selectively suppresses angiogenesis, growth and survival of human hepatocellular carcinoma

(2016) Yongdong Liu et al.   BIOMEDICINE & PHARMACOTHERAPY

Merestinib blocks Mnk kinase activity in acute myeloid leukemia progenitors and exhibits antileukemic effects in vitro and in vivo

(2016) E. M. Kosciuczuk et al.   BLOOD

Phosphorylation of eIF4E serine 209 is associated with tumour progression and reduced survival in malignant melanoma

(2016) Julia H Carter et al.   BRITISH JOURNAL OF CANCER

The MNK-1/eIF4E pathway as a new therapeutic pathway to target inflammation and remodelling in asthma

(2016) Petra Seidel et al.   CELLULAR SIGNALLING

Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy

(2016) Michal Grzmil et al.   CELLULAR SIGNALLING

Galeterone and VNPT55 disrupt Mnk-eIF4E to inhibit prostate cancer cell migration and invasion

(2016) Andrew K. Kwegyir-Afful et al.   FEBS Journal

Unveiling new chemical scaffolds as Mnk inhibitors

(2016) Sarah Diab et al.   Future Medicinal Chemistry

Discovery of a Selective and Potent Inhibitor of Mitogen-Activated Protein Kinase-Interacting Kinases 1 and 2 (MNK1/2) Utilizing Structure-Based Drug Design

(2016) Wooseok Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure–Activity Relationship Studies of Mitogen Activated Protein Kinase Interacting Kinase (MNK) 1 and 2 and BCR-ABL1 Inhibitors Targeting Chronic Myeloid Leukemic Cells

(2016) Joseph Cherian et al.   JOURNAL OF MEDICINAL CHEMISTRY

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Tuning Specific Translation in Cancer Metastasis and Synaptic Memory: Control at the MNK–eIF4E Axis

(2016) Clive R. Bramham et al.   TRENDS IN BIOCHEMICAL SCIENCES

CGP57380 enhances efficacy of RAD001 in non-small cell lung cancer through abrogating mTOR inhibition-induced phosphorylation of eIF4E and activating mitochondrial apoptotic pathway

(2016) Qiuyuan Wen et al.   Oncotarget

eIF4E promotes tumorigenesis and modulates chemosensitivity to cisplatin in esophageal squamous cell carcinoma

(2016) Ting Liu et al.   Oncotarget

Galeterone and its analogs inhibit Mnk-eIF4E axis, synergize with gemcitabine, impede pancreatic cancer cell migration, invasion and proliferation and inhibit tumor growth in mice

(2016) Andrew K. Kwegyir-Afful et al.   Oncotarget

MNK1 and MNK2 mediate adverse effects of high-fat feeding in distinct ways

(2016) C. E. J. Moore et al.   Scientific Reports

peIF4E as an independent prognostic factor and a potential therapeutic target in diffuse infiltrating astrocytomas

(2016) Elena Martínez-Sáez et al.   Cancer Medicine

The MAP kinase-interacting kinases regulate cell migration, vimentin expression and eIF4E/CYFIP1 binding

(2015) James E. Beggs et al.   BIOCHEMICAL JOURNAL

Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells

(2015) Theodosia Teo et al.   CANCER LETTERS

Androgen Receptor Modulation Optimized for Response (ARMOR) Phase I and II Studies: Galeterone for the Treatment of Castration-Resistant Prostate Cancer

(2015) B. Montgomery et al.   CLINICAL CANCER RESEARCH

An integrated approach for discovery of highly potent and selective Mnk inhibitors: Screening, synthesis and SAR analysis

(2015) Theodosia Teo et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 4-(dihydropyridinon-3-yl)amino-5-methylthieno[2,3-d]pyrimidine derivatives as potent Mnk inhibitors: synthesis, structure–activity relationship analysis and biological evaluation

(2015) Mingfeng Yu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Novel C-4 Heteroaryl 13-cis-Retinamide Mnk/AR Degrading Agents Inhibit Cell Proliferation and Migration and Induce Apoptosis in Human Breast and Prostate Cancer Cells and Suppress Growth of MDA-MB-231 Human Breast and CWR22Rv1 Human Prostate Tumor Xenografts in Mice

(2015) Hannah W. Mbatia et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Development of Galeterone (TOK-001 or VN/124-1) for the Treatment of All Stages of Prostate Cancer

(2015) Vincent C. O. Njar et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia

(2015) H Wu et al.   LEUKEMIA

Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation

(2015) Xiaodi Su et al.   NATURE IMMUNOLOGY

Simultaneous targeting of androgen receptor (AR) and MAPK-interacting kinases (MNKs) by novel retinamides inhibits growth of human prostate cancer cell lines

(2015) Vidya P. Ramamurthy et al.   Oncotarget

Discovery of 5-(2-(Phenylamino)pyrimidin-4-yl)thiazol-2(3H)-one Derivatives as Potent Mnk2 Inhibitors: Synthesis, SAR Analysis and Biological Evaluation

(2014) Sarah Diab et al.   ChemMedChem

Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3

(2014) N Robichaud et al.   ONCOGENE

MNK1-Induced eIF-4E Phosphorylation in Myeloma Cells: A Pathway Mediating IL-6-Induced Expansion and Expression of Genes Involved in Metabolic and Proteotoxic Responses

(2014) Yijiang Shi et al.   PLoS One

Inhibition of Mnk kinase activity by cercosporamide and suppressive effects on acute myeloid leukemia precursors

(2013) J. K. Altman et al.   BLOOD

Rational Design of Resorcylic Acid Lactone Analogues as Covalent MNK1/2 Kinase Inhibitors by Tuning the Reactivity of an Enamide Michael Acceptor

(2013) Jin Xu et al.   ChemMedChem

Translational control of human neutrophil responses by MNK1

(2013) Carl F. Fortin et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Targeting of the MNK-eIF4E axis in blast crisis chronic myeloid leukemia inhibits leukemia stem cell function

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

LY2801653 is an orally bioavailable multi-kinase inhibitor with potent activity against MET, MST1R, and other oncoproteins, and displays anti-tumor activities in mouse xenograft models

(2012) S. Betty Yan et al.   INVESTIGATIONAL NEW DRUGS

Translational control of the activation of transcription factor NF-κB and production of type I interferon by phosphorylation of the translation factor eIF4E

(2012) Barbara Herdy et al.   NATURE IMMUNOLOGY

Therapeutic Inhibition of MAP Kinase Interacting Kinase Blocks Eukaryotic Initiation Factor 4E Phosphorylation and Suppresses Outgrowth of Experimental Lung Metastases

(2011) B. W. Konicek et al.   CANCER RESEARCH

Exploring Aigialomycin D and Its Analogues as Protein Kinase Inhibitors for Cancer Targets

(2011) Jin Xu et al.   ACS Medicinal Chemistry Letters

Phosphorylated eukaryotic translation initiation factor 4 (eIF4E) is elevated in human cancer tissues

(2010) Songqing Fan et al.   CANCER BIOLOGY & THERAPY

Targeting the eIF4F translation initiation complex for cancer therapy

(2010) Bruce W. Konicek et al.   CELL CYCLE

Essential Role for Mnk Kinases in Type II Interferon (IFNγ) Signaling and Its Suppressive Effects on Normal Hematopoiesis

(2010) Sonali Joshi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Mitogen-Activated Protein Kinase-Interacting Kinase 1 Inhibitors by a Comprehensive Fragment-Oriented Virtual Screening Approach

(2010) Julen Oyarzabal et al.   JOURNAL OF MEDICINAL CHEMISTRY

Combined deficiency for MAP kinase-interacting kinase 1 and 2 (Mnk1 and Mnk2) delays tumor development

(2010) T. Ueda et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

(2010) L. Furic et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mnk earmarks eIF4E for cancer therapy

(2010) N. Hay   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

eIF4E Activation Is Commonly Elevated in Advanced Human Prostate Cancers and Significantly Related to Reduced Patient Survival

(2009) J. R. Graff et al.   CANCER RESEARCH

Type I interferon (IFN)-dependent activation of Mnk1 and its role in the generation of growth inhibitory responses

(2009) S. Joshi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phosphorylation of eIF4E by MNKs supports protein synthesis, cell cycle progression and proliferation in prostate cancer cells

(2008) Andrea Bianchini et al.   CARCINOGENESIS

The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases)

(2008) Maria Buxade   Frontiers in Bioscience-Landmark

Inhibition of Polysome Assembly Enhances Imatinib Activity against Chronic Myelogenous Leukemia and Overcomes Imatinib Resistance

(2008) M. Zhang et al.   MOLECULAR AND CELLULAR BIOLOGY

17 -Hydroxylase/17,20 lyase inhibitor VN/124-1 inhibits growth of androgen-independent prostate cancer cells via induction of the endoplasmic reticulum stress response

(2008) R. D. Bruno et al.   MOLECULAR CANCER THERAPEUTICS

A quantitative analysis of kinase inhibitor selectivity

(2008) Mazen W Karaman et al.   NATURE BIOTECHNOLOGY

MNK kinases regulate multiple TLR pathways and innate proinflammatory cytokines in macrophages

(2007) Robert M. Rowlett et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY