Non-kinase targets of protein kinase inhibitors

Chemical Proteomics Reveals Ferrochelatase as a Common Off-target of Kinase Inhibitors

(2016) Susan Klaeger et al.   ACS Chemical Biology

Validation and development of MTH1 inhibitors for treatment of cancer

(2016) U. Warpman Berglund et al.   ANNALS OF ONCOLOGY

Identification of potent and selective MTH1 inhibitors

(2016) Alessia Petrocchi et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

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

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

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

(2016) Peng Wu et al.   DRUG DISCOVERY TODAY

Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants

(2016) Hengmiao Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

(2016) Jason G. Kettle et al.   JOURNAL OF MEDICINAL CHEMISTRY

Feeling Nature’s PAINS: Natural Products, Natural Product Drugs, and Pan Assay Interference Compounds (PAINS)

(2016) Jonathan B. Baell   JOURNAL OF NATURAL PRODUCTS

The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

(2016) Gabriela Brumatti et al.   Science Translational Medicine

Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype

(2016) Feimeng Zheng et al.   Nature Communications

Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival

(2016) Tatsuro Kawamura et al.   Scientific Reports

Image-based compound profiling reveals a dual inhibitor of tyrosine kinase and microtubule polymerization

(2016) Kenji Tanabe   Scientific Reports

CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A

(2016) Jennifer Chu et al.   Cell Reports

Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2

(2016) Matej Janeček et al.   Scientific Reports

Parkinsonian toxin-induced oxidative stress inhibits basal autophagy in astrocytes via NQO2/quinone oxidoreductase 2: Implications for neuroprotection

(2015) Elzbieta Janda et al.   Autophagy

The problem of pyridinyl imidazole class inhibitors of MAPK14/p38α and MAPK11/p38β in autophagy research

(2015) Manoj B Menon et al.   Autophagy

Going for broke: targeting the human cancer pseudokinome

(2015) Fiona P. Bailey et al.   BIOCHEMICAL JOURNAL

Kinase and BET Inhibitors Together Clamp Inhibition of PI3K Signaling and Overcome Resistance to Therapy

(2015) Elias E. Stratikopoulos et al.   CANCER CELL

A Kinase-Independent Role for EGF Receptor in Autophagy Initiation

(2015) Xiaojun Tan et al.   CELL

Advancing Biological Understanding and Therapeutics Discovery with Small-Molecule Probes

(2015) Stuart L. Schreiber et al.   CELL

Activity-Based Protein Profiling: Recent Advances in Probe Development and Applications

(2015) Pengyu Yang et al.   CHEMBIOCHEM

Identifying Drug-Target Selectivity of Small-Molecule CRM1/XPO1 Inhibitors by CRISPR/Cas9 Genome Editing

(2015) Jasper E. Neggers et al.   CHEMISTRY & BIOLOGY

Extending kinome coverage by analysis of kinase inhibitor broad profiling data

(2015) Edgar Jacoby et al.   DRUG DISCOVERY TODAY

Structures of a diverse set of colchicine binding site inhibitors in complex with tubulin provide a rationale for drug discovery

(2015) Yuxi Wang et al.   FEBS Journal

Methyl 3-((6-Methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a Tubulin Polymerization Inhibitor Identified by MorphoBase and ChemProteoBase Profiling Methods

(2015) Hidemitsu Minegishi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity

(2015) Davide Carta et al.   JOURNAL OF MEDICINAL CHEMISTRY

Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: An expert consensus

(2015) Federico Cappuzzo et al.   LUNG CANCER

Comprehensive characterization of the Published Kinase Inhibitor Set

(2015) Jonathan M Elkins et al.   NATURE BIOTECHNOLOGY

Know your target, know your molecule

(2015) Mark E Bunnage et al.   Nature Chemical Biology

CRISPR-Cas9–based target validation for p53-reactivating model compounds

(2015) Michael Wanzel et al.   Nature Chemical Biology

Correlating chemical sensitivity and basal gene expression reveals mechanism of action

(2015) Matthew G Rees et al.   Nature Chemical Biology

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

The diverse role of RIP kinases in necroptosis and inflammation

(2015) John Silke et al.   NATURE IMMUNOLOGY

Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling

(2015) Kilian V M Huber et al.   NATURE METHODS

Thermal proteome profiling monitors ligand interactions with cellular membrane proteins

(2015) Friedrich B M Reinhard et al.   NATURE METHODS

Tackling reproducibility in academic preclinical drug discovery

(2015) Stephen V. Frye et al.   NATURE REVIEWS DRUG DISCOVERY

DYRK1A in neurodegeneration and cancer: Molecular basis and clinical implications

(2015) Ramzi Abbassi et al.   PHARMACOLOGY & THERAPEUTICS

Beating the odds: BETs in disease

(2015) Chen-Yi Wang et al.   TRENDS IN BIOCHEMICAL SCIENCES

RIPK1 and RIPK3: critical regulators of inflammation and cell death

(2015) Kim Newton   TRENDS IN CELL BIOLOGY

Antitumour potential of BPT: a dual inhibitor of cdk4 and tubulin polymerization

(2015) S Mahale et al.   Cell Death & Disease

Kinase-independent role for CRAF-driving tumour radioresistance via CHK2

(2015) Sunil J. Advani et al.   Nature Communications

Fluid shear triggers microvilli formation via mechanosensitive activation of TRPV6

(2015) Shigenori Miura et al.   Nature Communications

Harnessing Connectivity in a Large-Scale Small-Molecule Sensitivity Dataset

(2015) B. Seashore-Ludlow et al.   Cancer Discovery

Assessing the Efficacy of Mdm2/Mdm4-Inhibiting Stapled Peptides Using Cellular Thermal Shift Assays

(2015) Ban Xiong Tan et al.   Scientific Reports

Inhibition of Lapatinib-Induced Kinome Reprogramming in ERBB2-Positive Breast Cancer by Targeting BET Family Bromodomains

(2015) Timothy J. Stuhlmiller et al.   Cell Reports

ATP-Mediated Kinome Selectivity: The Missing Link in Understanding the Contribution of Individual JAK Kinase Isoforms to Cellular Signaling

(2014) Atli Thorarensen et al.   ACS Chemical Biology

Acetyl-lysine Binding Site of Bromodomain-Containing Protein 4 (BRD4) Interacts with Diverse Kinase Inhibitors

(2014) Stuart W. J. Ember et al.   ACS Chemical Biology

MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation

(2014) Enrico Desideri et al.   Autophagy

Structure of the BRAF-MEK Complex Reveals a Kinase Activity Independent Role for BRAF in MAPK Signaling

(2014) Jacob R. Haling et al.   CANCER CELL

Chemical biology approaches to target validation in cancer

(2014) Julian Blagg et al.   CURRENT OPINION IN PHARMACOLOGY

Cutting Edge: RIPK1 Kinase Inactive Mice Are Viable and Protected from TNF-Induced Necroptosis In Vivo

(2014) Apostolos Polykratis et al.   JOURNAL OF IMMUNOLOGY

Discovery of Biarylaminoquinazolines as Novel Tubulin Polymerization Inhibitors

(2014) Giovanni Marzaro et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tivantinib (ARQ 197) Exhibits Antitumor Activity by Directly Interacting with Tubulin and Overcomes ABC Transporter-Mediated Drug Resistance

(2014) A. Aoyama et al.   MOLECULAR CANCER THERAPEUTICS

RIP3 Induces Apoptosis Independent of Pronecrotic Kinase Activity

(2014) Pratyusha Mandal et al.   MOLECULAR CELL

Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy

(2014) Kilian V. M. Huber et al.   NATURE

MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool

(2014) Helge Gad et al.   NATURE

Chemistry: Chemical con artists foil drug discovery

(2014) Jonathan Baell et al.   NATURE

RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis

(2014) Marius Dannappel et al.   NATURE

DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells

(2014) Yegor Smurnyy et al.   Nature Chemical Biology

Dual kinase-bromodomain inhibitors for rationally designed polypharmacology

(2014) Pietro Ciceri et al.   Nature Chemical Biology

DrugTargetSeqR: a genomics- and CRISPR-Cas9–based method to analyze drug targets

(2014) Corynn Kasap et al.   Nature Chemical Biology

A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors

(2014) Bryan R Lanning et al.   Nature Chemical Biology

The cellular thermal shift assay for evaluating drug target interactions in cells

(2014) Rozbeh Jafari et al.   Nature Protocols

A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1

(2014) T. Justin Rettenmaier et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death

(2014) Joanne M. Hildebrand et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Tracking cancer drugs in living cells by thermal profiling of the proteome

(2014) M. M. Savitski et al.   SCIENCE

Activity of Protein Kinase RIPK3 Determines Whether Cells Die by Necroptosis or Apoptosis

(2014) K. Newton et al.   SCIENCE

A kinase-independent function of AKT promotes cancer cell survival

(2014) Igor Vivanco et al.   eLife

Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis

(2014) Scott J Dixon et al.   eLife

Microtubules and Their Role in Cellular Stress in Cancer

(2014) Amelia L. Parker et al.   Frontiers in Oncology

The Commonly Used PI3-Kinase Probe LY294002 Is an Inhibitor of BET Bromodomains

(2013) Antje Dittmann et al.   ACS Chemical Biology

Cyclin-Dependent Kinase Inhibitor Dinaciclib Interacts with the Acetyl-Lysine Recognition Site of Bromodomains

(2013) Mathew P. Martin et al.   ACS Chemical Biology

Comparison of Cancer Cell Survival Triggered by Microtubule Damage after Turning Dyrk1B Kinase On and Off

(2013) Liwen Li et al.   ACS Chemical Biology

Dawn of the dead: protein pseudokinases signal new adventures in cell biology

(2013) Patrick A. Eyers et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Cytotoxic Activity of Tivantinib (ARQ 197) Is Not Due Solely to c-MET Inhibition

(2013) R. Katayama et al.   CANCER RESEARCH

An Interactive Resource to Identify Cancer Genetic and Lineage Dependencies Targeted by Small Molecules

(2013) Amrita Basu et al.   CELL

Tivantinib (ARQ197) Displays Cytotoxic Activity That Is Independent of Its Ability to Bind MET

(2013) C. Basilico et al.   CLINICAL CANCER RESEARCH

NRH:Quinone Oxidoreductase 2 (NQO2) Protein Competes with the 20 S Proteasome to Stabilize Transcription Factor CCAAT Enhancer-binding Protein α (C/EBPα), Leading to Protection against γ Radiation-induced Myeloproliferative Disease

(2013) Junkang Xu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Selective 3-Phosphoinositide-Dependent Kinase 1 (PDK1) Inhibitors: Dissecting the Function and Pharmacology of PDK1

(2013) Jesús R. Medina   JOURNAL OF MEDICINAL CHEMISTRY

BET protein inhibition shows efficacy against JAK2V617F-driven neoplasms

(2013) B S Wyspiańska et al.   LEUKEMIA

Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis

(2013) Erik C Hett et al.   Nature Chemical Biology

Target identification and mechanism of action in chemical biology and drug discovery

(2013) Monica Schenone et al.   Nature Chemical Biology

Target validation using chemical probes

(2013) Mark E Bunnage et al.   Nature Chemical Biology

Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance

(2013) P. A. Schwartz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

(2013) D. M. Molina et al.   SCIENCE

RNA-Guided Human Genome Engineering via Cas9

(2013) P. Mali et al.   SCIENCE

Multiplex Genome Engineering Using CRISPR/Cas Systems

(2013) L. Cong et al.   SCIENCE

Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27

(2013) G Mellier et al.   Cell Death & Disease

MAPK14/p38α confers irinotecan resistance to TP53-defective cells by inducing survival autophagy

(2012) Salome Paillas et al.   Autophagy

Akt is efficiently activated by PIF-pocket- and PtdIns(3,4,5)P3-dependent mechanisms leading to resistance to PDK1 inhibitors

(2012) Ayaz Najafov et al.   BIOCHEMICAL JOURNAL

The Kynurenine Pathway in Brain Tumor Pathogenesis

(2012) S. Adams et al.   CANCER RESEARCH

Substrate-Selective Inhibition of Protein Kinase PDK1 by Small Compounds that Bind to the PIF-Pocket Allosteric Docking Site

(2012) Katrien Busschots et al.   CHEMISTRY & BIOLOGY

Indoleamine 2,3-dioxygenase: From catalyst to signaling function

(2012) Francesca Fallarino et al.   EUROPEAN JOURNAL OF IMMUNOLOGY

Chemistry-based functional proteomics for drug target deconvolution

(2012) Kui Wang et al.   Expert Review of Proteomics

Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks

(2012) Tjeerd Barf et al.   JOURNAL OF MEDICINAL CHEMISTRY

Using transcriptome sequencing to identify mechanisms of drug action and resistance

(2012) Sarah A Wacker et al.   Nature Chemical Biology

Reducing safety-related drug attrition: the use of in vitro pharmacological profiling

(2012) Joanne Bowes et al.   NATURE REVIEWS DRUG DISCOVERY

Kinase-independent function of checkpoint kinase 1 (Chk1) in the replication of damaged DNA

(2012) J. Speroni et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

BRD4 is an atypical kinase that phosphorylates Serine2 of the RNA Polymerase II carboxy-terminal domain

(2012) B. N. Devaiah et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity

(2012) M. Jinek et al.   SCIENCE

Necrostatin-1 analogues: critical issues on the specificity, activity and in vivo use in experimental disease models

(2012) N Takahashi et al.   Cell Death & Disease

The Evolution of Protein Kinase Inhibitors from Antagonists to Agonists of Cellular Signaling

(2011) Arvin C. Dar et al.   Annual Review of Biochemistry

Induction of autophagy in hepatocellular carcinoma cells by SB203580 requires activation of AMPK and DAPK but not p38 MAPK

(2011) Haitao Zhang et al.   APOPTOSIS

PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models

(2011) K. Ellwood-Yen et al.   CANCER RESEARCH

The secret life of kinases: functions beyond catalysis

(2011) Jens Rauch et al.   Cell Communication and Signaling

High-Throughput Kinase Profiling: A More Efficient Approach toward the Discovery of New Kinase Inhibitors

(2011) Chandrasekhar V. Miduturu et al.   CHEMISTRY & BIOLOGY

Discovery of a Novel Mode of Protein Kinase Inhibition Characterized by the Mechanism of Inhibition of Human Mesenchymal-epithelial Transition Factor (c-Met) Protein Autophosphorylation by ARQ 197

(2011) Sudharshan Eathiraj et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Comprehensive analysis of kinase inhibitor selectivity

(2011) Mindy I Davis et al.   NATURE BIOTECHNOLOGY

A MEK-independent role for CRAF in mitosis and tumor progression

(2011) Ainhoa Mielgo et al.   NATURE MEDICINE

Mitosis is not a key target of microtubule agents in patient tumors

(2011) Edina Komlodi-Pasztor et al.   Nature Reviews Clinical Oncology

P38MAPK is a major determinant of the balance between apoptosis and autophagy triggered by 5-fluorouracil: implication in resistance

(2011) M A de la Cruz-Morcillo et al.   ONCOGENE

IC261 induces cell cycle arrest and apoptosis of human cancer cells via CK1δ/ɛ and Wnt/β-catenin independent inhibition of mitotic spindle formation

(2011) J K Cheong et al.   ONCOGENE

SB202190-Induced Cell Type-Specific Vacuole Formation and Defective Autophagy Do Not Depend on p38 MAP Kinase Inhibition

(2011) Manoj B. Menon et al.   PLoS One

TG101209, a novel JAK2 inhibitor, has significant in vitro activity in multiple myeloma and displays preferential cytotoxicity for CD45+ myeloma cells

(2010) Vijay Ramakrishnan et al.   AMERICAN JOURNAL OF HEMATOLOGY

Fluorescence polarization binding assay to develop inhibitors of inactive p38α mitogen-activated protein kinase

(2010) Lenka Munoz et al.   ANALYTICAL BIOCHEMISTRY

EGFR and EGFRvIII interact with PUMA to inhibit mitochondrial translocalization of PUMA and PUMA-mediated apoptosis independent of EGFR kinase activity

(2010) Hu Zhu et al.   CANCER LETTERS

Application of Proteomic Profiling Based on 2D-DIGE for Classification of Compounds According to the Mechanism of Action

(2010) Makoto Muroi et al.   CHEMISTRY & BIOLOGY

Enhanced Indoleamine 2,3‐Dioxygenase Activity in Patients with Severe Sepsis and Septic Shock

(2010) Pierre Tattevin et al.   JOURNAL OF INFECTIOUS DISEASES

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

(2010) Jonathan B. Baell et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Benzothiophene Inhibitor of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Inhibits Tumor Necrosis Factor   Production and Has Oral Anti-Inflammatory Efficacy in Acute and Chronic Models of Inflammation

(2010) R. J. Mourey et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity

(2010) N. Munshi et al.   MOLECULAR CANCER THERAPEUTICS

Dinaciclib (SCH 727965), a Novel and Potent Cyclin-Dependent Kinase Inhibitor

(2010) David Parry et al.   MOLECULAR CANCER THERAPEUTICS

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

A genetically selective inhibitor demonstrates a function for the kinase Zap70 in regulatory T cells independent of its catalytic activity

(2010) Byron B Au-Yeung et al.   NATURE IMMUNOLOGY

Microtubule-binding agents: a dynamic field of cancer therapeutics

(2010) Charles Dumontet et al.   NATURE REVIEWS DRUG DISCOVERY

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

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

LY303511 Enhances TRAIL Sensitivity of SHEP-1 Neuroblastoma Cells via Hydrogen Peroxide-Mediated Mitogen-Activated Protein Kinase Activation and Up-regulation of Death Receptors

(2009) K. Shenoy et al.   CANCER RESEARCH

Coordinated regulation of autophagy by p38α MAPK through mAtg9 and p38IP

(2009) Jemma L Webber et al.   EMBO JOURNAL

Blockade of Indoleamine 2,3-Dioxygenase Protects Mice against Lipopolysaccharide-Induced Endotoxin Shock

(2009) I. D. Jung et al.   JOURNAL OF IMMUNOLOGY

Selective Inhibition of Casein Kinase 1  Minimally Alters Circadian Clock Period

(2009) K. M. Walton et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Erythropoietic protoporphyria

(2009) Mario Lecha et al.   Orphanet Journal of Rare Diseases

The structure of the leukemia drug imatinib bound to human quinone reductase 2 (NQO2)

(2009) Jonathan A Winger et al.   BMC STRUCTURAL BIOLOGY

Survival of Cancer Cells Is Maintained by EGFR Independent of Its Kinase Activity

(2008) Zhang Weihua et al.   CANCER CELL

Efficacy of TG101348, a Selective JAK2 Inhibitor, in Treatment of a Murine Model of JAK2V617F-Induced Polycythemia Vera

(2008) Gerlinde Wernig et al.   CANCER CELL

Anti-apoptotic and growth-stimulatory functions of CK1 delta and epsilon in ductal adenocarcinoma of the pancreas are inhibited by IC261 in vitro and in vivo

(2008) C Brockschmidt et al.   GUT

Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitors

(2008) P. Ross-Macdonald et al.   MOLECULAR CANCER THERAPEUTICS

Identification of RIP1 kinase as a specific cellular target of necrostatins

(2008) Alexei Degterev et al.   Nature Chemical Biology