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Development and Therapeutic Potential of NUAKs Inhibitors

https://doi.org/10.1021/acs.jmedchem.0c00533

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What this work says

Outgoing claims: the papers this work cites, builds on, or argues with.

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A new serine/threonine protein kinase, Omphk1, essential to ventral body wall formation

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Neural tube defects by NUAK1 and NUAK2 double mutation

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Hoxb2 and Hoxb4 Act Together to Specify Ventral Body Wall Formation

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Regulation of skeletal muscle sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase (SNARK) by metabolic stress and diabetes

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Expression level of NUAK1 in human nasopharyngeal carcinoma and its prognostic significance

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Tgfß2 -/- Tgfß3 -/- double knockout mice display severe midline fusion defects and early embryonic lethality

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ARK5 is associated with the invasive and metastatic potential of human breast cancer cells

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Overexpression of NUAK1 is associated with disease-free survival and overall survival in patients with gastric cancer

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Overexpression of ARK5 is associated with poor prognosis in hepatocellular carcinoma

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Regulation of SNARK activity in response to cellular stresses

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The LKB1 tumor suppressor kinase in human disease

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Induction of cell–cell detachment during glucose starvation through F-actin conversion by SNARK, the fourth member of the AMP-activated protein kinase catalytic subunit family

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Identification of a novel substrate for TNFα-induced kinase NUAK2

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MiR-145 functions as a tumor suppressor targeting NUAK1 in human intrahepatic cholangiocarcinoma

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Discovery of a potent inhibitor of MELK that inhibits expression of the anti-apoptotic protein Mcl-1 and TNBC cell growth

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Structure-based design and development of (benz)imidazole pyridones as JAK1-selective kinase inhibitors

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ARK5 promotes doxorubicin resistance in hepatocellular carcinoma via epithelial–mesenchymal transition

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The CREB Coactivator TORC2 Functions as a Calcium- and cAMP-Sensitive Coincidence Detector

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Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals

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Terminal Axon Branching Is Regulated by the LKB1-NUAK1 Kinase Pathway via Presynaptic Mitochondrial Capture

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Energy Stress Regulates Hippo-YAP Signaling Involving AMPK-Mediated Regulation of Angiomotin-like 1 Protein

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The Hippo Signaling Pathway in Development and Cancer

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Small-molecule kinase inhibitors: an analysis of FDA-approved drugs

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ARK5 promotes glioma cell invasion, and its elevated expression is correlated with poor clinical outcome

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Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription

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Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model

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Comparison of the specificity of Trk inhibitors in recombinant and neuronal assays

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The tau of MARK: a polarized view of the cytoskeleton

inferredcites →https://doi.org/10.1016/j.ydbio.2003.11.021openalex-snapshot

Loss of AP-2α impacts multiple aspects of ventral body wall development and closure

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Requirement for Mab21l2 during development of murine retina and ventral body wall

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ARK5 Expression in Colorectal Cancer and Its Implications for Tumor Progression

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Protein kinases and protein phosphatases in prokaryotes: a genomic perspective

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Discovery of an Orally Efficacious Inhibitor of Anaplastic Lymphoma Kinase

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Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3- d ]pyrimidine-6-carbonitrile ( 7x ) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

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UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

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Omphalocele in trisomy 3q: further delineation of phenotype

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MiR-204 inhibits human NSCLC metastasis through suppression of NUAK1

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Regulation of ploidy and senescence by the AMPK‐related kinase NUAK1

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Another fork in the road—life or death decisions by the tumour suppressor p53

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Transcription Factor/microRNA Axis Blocks Melanoma Invasion Program by miR-211 Targeting NUAK1

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Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348)

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Deregulated MYC expression induces dependence upon AMPK-related kinase 5

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Comprehensive analysis of kinase inhibitor selectivity

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A quantitative analysis of kinase inhibitor selectivity

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Mitogenic signalling and the p16INK4a–Rb pathway cooperate to enforce irreversible cellular senescence

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A genetic screen identifies an LKB1–MARK signalling axis controlling the Hippo–YAP pathway

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Cellular energy stress induces AMPK-mediated regulation of YAP and the Hippo pathway

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AMPK modulates Hippo pathway activity to regulate energy homeostasis

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Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

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AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy

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AMPK: a nutrient and energy sensor that maintains energy homeostasis

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A new role of NUAK1: directly phosphorylating p53 and regulating cell proliferation

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LKB1 tumor suppressor regulates AMP kinase/mTOR-independent cell growth and proliferation via the phosphorylation of Yap

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Calcium signalling links MYC to NUAK1

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A feed forward loop enforces YAP/TAZ signaling during tumorigenesis

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Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice

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NUAK2 is a critical YAP target in liver cancer

inferredcites →https://doi.org/10.1038/sj.emboj.7600110openalex-snapshot

LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR‐1

inferredcites →https://doi.org/10.1038/sj.onc.1206899openalex-snapshot

ARK5 suppresses the cell death induced by nutrient starvation and death receptors via inhibition of caspase 8 activation, but not by chemotherapeutic agents or UV irradiation

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Identification and characterization of a novel sucrose-non-fermenting protein kinase/AMP-activated protein kinase-related protein kinase, SNARK

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Characterization of WZ4003 and HTH-01-015 as selective inhibitors of the LKB1-tumour-suppressor-activated NUAK kinases

inferredcites →https://doi.org/10.1042/bj20140408openalex-snapshot

Interplay between Polo kinase, LKB1-activated NUAK1 kinase, PP1βMYPT1 phosphatase complex and the SCFβTrCP E3 ubiquitin ligase

inferredcites →https://doi.org/10.1073/pnas.1008131107openalex-snapshot

Sucrose nonfermenting AMPK-related kinase (SNARK) mediates contraction-stimulated glucose transport in mouse skeletal muscle

inferredcites →https://doi.org/10.1073/pnas.1019559108openalex-snapshot

Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK

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Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages

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Use of the Pharmacological Inhibitor BX795 to Study the Regulation and Physiological Roles of TBK1 and IκB Kinase ϵ

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Muscle-specific Knock-out of NUAK Family SNF1-like Kinase 1 (NUAK1) Prevents High Fat Diet-induced Glucose Intolerance

inferredcites →https://doi.org/10.1074/jbc.m206025200openalex-snapshot

Identification of a Novel Protein Kinase Mediating Akt Survival Signaling to the ATM Protein

inferredcites →https://doi.org/10.1074/jbc.m306205200openalex-snapshot

Knockout of the α2 but Not α1 5′-AMP-activated Protein Kinase Isoform Abolishes 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranosidebut Not Contraction-induced Glucose Uptake in Skeletal Muscle

inferredcites →https://doi.org/10.1074/jbc.m404334200openalex-snapshot

Identification of SNF1/AMP Kinase-related Kinase as an NF-κB-regulated Anti-apoptotic Kinase Involved in CD95-induced Motility and Invasiveness

inferredcites →https://doi.org/10.1074/jbc.m501367200openalex-snapshot

Novel Small Molecule Inhibitors of 3-Phosphoinositide-dependent Kinase-1

inferredcites →https://doi.org/10.1074/jbc.m504208200openalex-snapshot

AMP-activated Protein Kinase α2 Activity Is Not Essential for Contraction- and Hyperosmolarity-induced Glucose Transport in Skeletal Muscle

inferredcites →https://doi.org/10.1074/jbc.m506863200openalex-snapshot

M-RIP Targets Myosin Phosphatase to Stress Fibers to Regulate Myosin Light Chain Phosphorylation in Vascular Smooth Muscle Cells

inferredcites →https://doi.org/10.1074/jbc.m803813200openalex-snapshot

Effects of the JAK2 Inhibitor, AZ960, on Pim/BAD/BCL-xL Survival Signaling in the Human JAK2 V617F Cell Line SET-2

inferredcites →https://doi.org/10.1074/jbc.ra118.004984openalex-snapshot

Transforming growth factor β (TGFβ) induces NUAK kinase expression to fine-tune its signaling output

inferredcites →https://doi.org/10.1080/10408398.2010.500245openalex-snapshot

Cross-Talk between AMPK and mTOR in Regulating Energy Balance

inferredcites →https://doi.org/10.1083/jcb.201806065openalex-snapshot

YAP and TAZ limit cytoskeletal and focal adhesion maturation to enable persistent cell motility

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A Novel Regulatory Mechanism of Myosin Light Chain Phosphorylation via Binding of 14-3-3 to Myosin Phosphatase

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Risk Prediction for Late-Stage Ovarian Cancer by Meta-analysis of 1525 Patient Samples

inferredcites →https://doi.org/10.1096/fj.09-148064openalex-snapshot

Structure and function of polarity‐inducing kinase family MARK/Par‐1 within the branch of AMPK/Snf1‐related kinases

inferredcites →https://doi.org/10.1111/febs.13534openalex-snapshot

Evidence of cancer‐promoting roles for AMPK and related kinases

inferredcites →https://doi.org/10.1111/j.1349-7006.2008.00734.xopenalex-snapshot

Susceptibility of Snark‐deficient mice to azoxymethane‐induced colorectal tumorigenesis and the formation of aberrant crypt foci

inferredcites →https://doi.org/10.1111/j.1365-2443.2005.00882.xopenalex-snapshot

ROCK‐I and ROCK‐II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo

inferredcites →https://doi.org/10.1111/jcmm.13497openalex-snapshot

LncRNA SNHG1 functions as a ceRNA to antagonize the effect of miR‐145a‐5p on the down‐regulation of NUAK1 in nasopharyngeal carcinoma cell

inferredcites →https://doi.org/10.1124/jpet.114.218164openalex-snapshot

The Novel Kinase Inhibitor PRT062070 (Cerdulatinib) Demonstrates Efficacy in Models of Autoimmunity and B-Cell Cancer

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Mammalian SAD Kinases Are Required for Neuronal Polarization

inferredcites →https://doi.org/10.1126/science.1112014openalex-snapshot

The Transcriptional Landscape of the Mammalian Genome

inferredcites →https://doi.org/10.1126/science.3291115openalex-snapshot

The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains

inferredcites →https://doi.org/10.1126/scisignal.2000616openalex-snapshot

New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion

inferredcites →https://doi.org/10.1128/mcb.00979-06openalex-snapshot

Skeletal Muscle-Selective Knockout of LKB1 Increases Insulin Sensitivity, Improves Glucose Homeostasis, and Decreases TRB3

inferredcites →https://doi.org/10.1128/mcb.24.8.3526-3535.2004openalex-snapshot

ARK5 Is a Tumor Invasion-Associated Factor Downstream of Akt Signaling

inferredcites →https://doi.org/10.1136/jmg.39.3.184openalex-snapshot

Omphalocele in three generations with autosomal dominant transmission: Figure 1

inferredcites →https://doi.org/10.1146/annurev.med.49.1.235openalex-snapshot

Exercise, Glucose Transport, and Insulin Sensitivity

inferredcites →https://doi.org/10.1152/advan.00080.2014openalex-snapshot

Exercise and type 2 diabetes: molecular mechanisms regulating glucose uptake in skeletal muscle

inferredcites →https://doi.org/10.1152/ajpendo.00335.2004openalex-snapshot

Muscle contractions, AICAR, and insulin cause phosphorylation of an AMPK-related kinase

inferredcites →https://doi.org/10.1152/ajprenal.1997.273.2.f283openalex-snapshot

Role of Rho and myosin phosphorylation in actin stress fiber assembly in mesangial cells

inferredcites →https://doi.org/10.1152/physiolgenomics.00200.2010openalex-snapshot

Identification and prioritization ofNUAK1andPPP1CCas positional candidate loci for skeletal muscle strength phenotypes

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Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma

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BAY 1000394, a Novel Cyclin-Dependent Kinase Inhibitor, with Potent Antitumor Activity in Mono- and in Combination Treatment upon Oral Application

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Biological Characterization of TAK-901, an Investigational, Novel, Multitargeted Aurora B Kinase Inhibitor

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Preclinical Pharmacological Evaluation of a Novel Multiple Kinase Inhibitor, ON123300, in Brain Tumor Models

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LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms

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BI 885578, a Novel IGF1R/INSR Tyrosine Kinase Inhibitor with Pharmacokinetic Properties That Dissociate Antitumor Efficacy and Perturbation of Glucose Homeostasis

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Abstract 2133: Ending the endless acquired tyrosine kinase resistance mutations — Design of TPX-0005, a multi-target ALK/ROS1/TRK inhibitor with broad spectrum activity against wild-type and mutants including ALK G1202R, ROS1 G2032R and TRKA G595R

inferredcites →https://doi.org/10.1158/2159-8290.cd-17-0533openalex-snapshot

Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress

inferredcites →https://doi.org/10.1159/000478685openalex-snapshot

Knockdown of ARK5 Expression Suppresses Invasion and Metastasis of Gastric Cancer

inferredcites →https://doi.org/10.1161/circresaha.108.188524openalex-snapshot

ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle Cells

inferredcites →https://doi.org/10.1172/jci79197openalex-snapshot

The AMPK-related kinase SNARK regulates muscle mass and myocyte survival

inferredcites →https://doi.org/10.1182/blood.v120.21.2764.2764openalex-snapshot

PRT062070: A Dual Syk/JAK Inhibitor with Potent Immune Regulatory Capacity in Rodent Models of Inflammation and Cancer.

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The repertoire of protein kinases encoded in the draft version of the human genome: atypical variations and uncommon domain combinations

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Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer

inferredcites →https://doi.org/10.1242/jcs.072660openalex-snapshot

An association between NUAK2 and MRIP reveals a novel mechanism for regulation of actin stress fibers

inferredcites →https://doi.org/10.1371/journal.pgen.1008700openalex-snapshot

Drosophila NUAK functions with Starvin/BAG3 in autophagic protein turnover

inferredcites →https://doi.org/10.1517/17460441.3.6.607openalex-snapshot

The challenge of selecting protein kinase assays for lead discovery optimization

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Caenorhabditis elegans unc-82 Encodes a Serine/Threonine Kinase Important for Myosin Filament Organization in Muscle During Growth

inferredcites →https://doi.org/10.18632/oncotarget.4158openalex-snapshot

Discovery of benzo[e]pyridoindolones as kinase inhibitors that disrupt mitosis exit while erasing AMPK-Thr172 phosphorylation on the spindle

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microRNA-203 suppresses invasion and epithelial-mesenchymal transition induction via targeting NUAK1 in head and neck cancer

inferredcites →https://doi.org/10.21954/ou.ro.0000e44copenalex-snapshot

Dissecting Melanoma Heterogeneity by Integrative Genomic Analysis for Tailored Anti-Cancer Therapy

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LKB1 Regulates Lipid Oxidation During Exercise Independently of AMPK

inferredcites →https://doi.org/10.24297/jac.v11i8.2193openalex-snapshot

SYNTHESIS AND NMR SPECTRAL CHARACTERIZATION OF NOVEL 2,3-POLYMETHYLENEPYRIDO[2,3-D]PYRIMIDIN-4-ONES

inferredcites →https://doi.org/10.24959/ophcj.18.935openalex-snapshot

The study of the interaction of 4,6-dichloropyrimidine-5-carbaldehyde with glycine esters

inferredcites →https://doi.org/10.25560/23995openalex-snapshot

Investigating the role and regulation of the AMPK-related kinase NUAK1

inferredcites →https://doi.org/10.3109/01902148.2012.744115openalex-snapshot

High NUAK1 expression correlates with poor prognosis and involved in NSCLC cells migration and invasion

inferredcites →https://doi.org/10.3389/fonc.2016.00213openalex-snapshot

NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer

inferredcites →https://doi.org/10.3892/ijmm.2014.1940openalex-snapshot

miR-96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer

inferredcites →https://doi.org/10.3892/mmr.2017.7970openalex-snapshot

TGF‑β signaling: A complex role in tumorigenesis (Review)

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Activation of ARK5/miR-1181/HOXA10 axis promotes epithelial-mesenchymal transition in ovarian cancer

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Regulation and Function of Protein Kinases and Phosphatases

What points at this work

Incoming claims: where this work appears in other papers’ reference lists and arguments.

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Enantioselective Construction of Bridged Biaryl Atropisomers With Medium‐ and Macrocyclic Architectures

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The ARK side of the cell: Kinases, metabolism, and therapeutic potential in malignancies

inferred← citeshttps://doi.org/10.1016/j.xcrm.2024.101913openalex-snapshot

Targeting the mevalonate pathway potentiates NUAK1 inhibition-induced immunogenic cell death and antitumor immunity

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.1c00440openalex-snapshot

Identification of Pyrimidine-Based Lead Compounds for Understudied Kinases Implicated in Driving Neurodegeneration

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.4c01237openalex-snapshot

Discovery of UCB9386: A Potent, Selective, and Brain-Penetrant Nuak1 Inhibitor Suitable for In Vivo Pharmacological Studies

inferred← citeshttps://doi.org/10.1021/acs.jmedchem.5c03079openalex-snapshot

Structure-Based Design of Potent and Highly Selective NUAK1 Inhibitors by Exploiting a Unique Glutamate Switch for the Prevention of Tumor Growth, Migration, and Invasion

inferred← citeshttps://doi.org/10.1021/acsmedchemlett.4c00579openalex-snapshot

Development of the Pyrido[2,3- d ]pyrimidin-7(8 H )-one Scaffold toward Potent and Selective NUAK1 Inhibitors

inferred← citeshttps://doi.org/10.1021/acsmedchemlett.5c00467openalex-snapshot

Development of Purine and Pyrrolopyrimidine Scaffolds as Potent, Selective, and Brain Penetrant NUAK1 Inhibitors

inferred← citeshttps://doi.org/10.1038/s41467-024-55706-9openalex-snapshot

Genome-wide association study unravels mechanisms of brain glymphatic activity

inferred← citeshttps://doi.org/10.1039/d1nj03690dopenalex-snapshot

Homology modeling, virtual screening and MD simulations for the identification of NUAK1 and ULK1 potential dual inhibitors

inferred← citeshttps://doi.org/10.1042/ebc20240005openalex-snapshot

NUAK: never underestimate a kinase

inferred← citeshttps://doi.org/10.1101/2024.12.19.629332openalex-snapshot

NUAK1 regulates contraction in vascular smooth muscle cells derived from abdominal aortic aneurysm patients

inferred← citeshttps://doi.org/10.1186/s10020-025-01088-7openalex-snapshot

NUAK1 acts as a novel regulator of PD-L1 via activating GSK-3β/β-catenin pathway in hepatocellular carcinoma

inferred← citeshttps://doi.org/10.1186/s12864-023-09569-xopenalex-snapshot

The role of antifreeze genes in the tolerance of cold stress in the Nile tilapia (Oreochromis niloticus)

inferred← citeshttps://doi.org/10.1186/s13578-023-01185-2openalex-snapshot

NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling

inferred← citeshttps://doi.org/10.2337/db25-0417openalex-snapshot

NUAK1 Promotes Diabetic Kidney Disease by Accelerating Renal Tubular Senescence via the ROS/P53 Axis

inferred← citeshttps://doi.org/10.26434/chemrxiv.14195207openalex-snapshot

Strategy for Lead Identification for Understudied Kinases

inferred← citeshttps://doi.org/10.3389/fphar.2023.1105427openalex-snapshot

Inhibition of growth and contraction in human prostate stromal cells by silencing of NUAK1 and -2, and by the presumed NUAK inhibitors HTH01-015 and WZ4003

inferred← citeshttps://doi.org/10.3390/cancers13133377openalex-snapshot

NUAK1 and NUAK2 Fine-Tune TGF-β Signaling

inferred← citeshttps://doi.org/10.3390/ijms23158768openalex-snapshot

Multitargeting the Action of 5-HT6 Serotonin Receptor Ligands by Additional Modulation of Kinases in the Search for a New Therapy for Alzheimer’s Disease: Can It Work from a Molecular Point of View?

inferred← citeshttps://doi.org/10.3390/ijms232113084openalex-snapshot

Enhanced Expression of ARK5 in Hepatic Stellate Cell and Hepatocyte Synergistically Promote Liver Fibrosis

inferred← citeshttps://doi.org/10.6084/m9.figshare.26657482openalex-snapshot

Additional file 1 of NUAK1 coordinates growth factor-dependent activation of mTORC2 and Akt signaling

inferred← citeshttps://doi.org/10.70675/247335b1zba7fz4005zafbdzdc43c088d75fopenalex-snapshot

Bases métaboliques du développement neuronal : rôles de la kinase NUAK1 dans la régulation des mitochondries axonales

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