Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets

A scaffold-hopping approach to discover potent, selective and efficacious inhibitors of NF-κB inducing kinase

(2018) Nicole Blaquiere et al.   JOURNAL OF MEDICINAL CHEMISTRY

Role of the NFκB-signaling pathway in cancer

(2018) Longzheng Xia et al.   OncoTargets and Therapy

The Prognostic Role of the Non-Canonical Nuclear Factor-Kappa B Pathway in Renal Cell Carcinoma Patients

(2018) Joanne Lua et al.   UROLOGIA INTERNATIONALIS

High IKKα expression is associated with reduced time to recurrence and cancer specific survival in oestrogen receptor (ER)-positive breast cancer

(2017) Lindsay Bennett et al.   INTERNATIONAL JOURNAL OF CANCER

Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers

(2017) Nahoum G. Anthony et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure-Based Design of Tricyclic NF-κB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K)

(2017) Georgette M. Castanedo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Predictive Biomarkers for Endocrine Therapy: Retrospective Study in Tamoxifen and Exemestane Adjuvant Multinational (TEAM) Trial

(2017) Antonia K Roseweir et al.   JNCI-Journal of the National Cancer Institute

Predictive Biomarkers for Endocrine Therapy: Retrospective Study in Tamoxifen and Exemestane Adjuvant Multinational (TEAM) Trial

(2017) Antonia K Roseweir et al.   JNCI-Journal of the National Cancer Institute

Importance of the alternative NF-κB activation pathway in inflammation-associated gastrointestinal carcinogenesis

(2016) Yvette J. Merga et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells

(2016) Zhen Yang et al.   BRITISH JOURNAL OF CANCER

Chronic lymphocytic leukaemia

(2016) Lydia Scarfò et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

NF-κB deregulation in splenic marginal zone lymphoma

(2016) Valeria Spina et al.   SEMINARS IN CANCER BIOLOGY

Noncanonical NF-κB Signaling in Health and Disease

(2016) Gökhan Cildir et al.   TRENDS IN MOLECULAR MEDICINE

PI3K/Akt promotes feedforward mTORC2 activation through IKKα

(2016) Han C. Dan et al.   Oncotarget

LGR5 expression is controled by IKKα in basal cell carcinoma through activating STAT3 signaling pathway

(2016) Jiantao Jia et al.   Oncotarget

Prognostic significance of RelB overexpression in non-small cell lung cancer patients

(2016) Hualong Qin et al.   Thoracic Cancer

Structural Basis for the Activation of IKK1/α

(2016) Smarajit Polley et al.   Cell Reports

NIK regulates MT1-MMP activity and promotes glioma cell invasion independently of the canonical NF-κB pathway

(2016) C L Duran et al.   Oncogenesis

Downregulation of miR-518a-3p activates the NIK-dependent NF-κB pathway in colorectal cancer

(2015) L.L. QU et al.   INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE

Functional loss of IκBε leads to NF-κB deregulation in aggressive chronic lymphocytic leukemia

(2015) Larry Mansouri et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Deleted in Breast Cancer 1 Suppresses B Cell Activation through RelB and Is Regulated by IKKα Phosphorylation

(2015) Sinyi Kong et al.   JOURNAL OF IMMUNOLOGY

Non-canonical NF-κB signalling and ETS1/2 cooperatively drive C250T mutant TERT promoter activation

(2015) Yinghui Li et al.   NATURE CELL BIOLOGY

BRAF-induced tumorigenesis is IKKα-dependent but NF-κB–independent

(2015) Pol Margalef et al.   Science Signaling

Apigenin blocks IKKα activation and suppresses prostate cancer progression

(2015) Sanjeev Shukla et al.   Oncotarget

An Oncogenic Role for Alternative NF-κB Signaling in DLBCL Revealed upon Deregulated BCL6 Expression

(2015) Baochun Zhang et al.   Cell Reports

BRAF-induced tumorigenesis is IKKα-dependent but NF-κB–independent

(2015) Pol Margalef et al.   Science Signaling

Suppression of NF-κB and NF-κB-Regulated Gene Expression by Apigenin through IκBα and IKK Pathway in TRAMP Mice

(2015) Sanjeev Shukla et al.   PLoS One

IκB Kinases Modulate the Activity of the Androgen Receptor in Prostate Carcinoma Cell Lines

(2015) Garima Jain et al.   NEOPLASIA

Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib

(2014) D. Wodarz et al.   BLOOD

Recurrent mutations refine prognosis in chronic lymphocytic leukemia

(2014) P Baliakas et al.   LEUKEMIA

NOTCH1, SF3B1, BIRC3andTP53mutations in patients with chronic lymphocytic leukemia undergoing first-line treatment: correlation with biological parameters and response to treatment

(2014) Sabina Chiaretti et al.   LEUKEMIA & LYMPHOMA

Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner

(2014) MO SHEN et al.   Molecular Medicine Reports

AI-06 * NON-CANONICAL NF-kB SIGNALING DRIVES THE AGGRESSIVE INVASIVENESS OF GLIOBLASTOMA

(2014) E. Cherry et al.   NEURO-ONCOLOGY

Non-conventional functions for NF-κB members: the dark side of NF-κB

(2014) L Espinosa et al.   ONCOGENE

Tissue injury and hypoxia promote malignant progression of prostate cancer by inducing CXCL13 expression in tumor myofibroblasts

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

Regulation of p53 and Rb Links the Alternative NF-κB Pathway to EZH2 Expression and Cell Senescence

(2014) Alessio Iannetti et al.   PLoS Genetics

NFκB regulates expression of Polo-like kinase 4

(2013) Adeline Ledoux et al.   CELL CYCLE

An IKK -E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence

(2013) M. Ammirante et al.   GENES & DEVELOPMENT

Crystal Structure of a Human IκB Kinase β Asymmetric Dimer

(2013) Shenping Liu et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Proteasome Inhibition by Bortezomib Increases IL-8 Expression in Androgen-Independent Prostate Cancer Cells: The Role of IKK 

(2013) S. Manna et al.   JOURNAL OF IMMUNOLOGY

The role of tumour–stromal interactions in modifying drug response: challenges and opportunities

(2013) Douglas W. McMillin et al.   NATURE REVIEWS DRUG DISCOVERY

Deficiency of Innate and Acquired Immunity Caused by an IKBKB Mutation

(2013) Ulrich Pannicke et al.   NEW ENGLAND JOURNAL OF MEDICINE

Downregulation of TRAF2 Mediates NIK-Induced Pancreatic Cancer Cell Proliferation and Tumorigenicity

(2013) Heike Döppler et al.   PLoS One

A Structural Basis for IκB Kinase 2 Activation Via Oligomerization-Dependent Trans Auto-Phosphorylation

(2013) Smarajit Polley et al.   PLOS BIOLOGY

Characterization of the Inhibitor of KappaB Kinase (IKK) Complex in Granulosa Cell Tumors of the Ovary and Granulosa Cell Tumor-Derived Cell Lines

(2013) Stacey Jamieson et al.   Hormones & Cancer

The noncanonical NF-κB pathway

(2012) Shao-Cong Sun   IMMUNOLOGICAL REVIEWS

Understanding NIK Regulation from Its Structure

(2012) Zhihua Tao et al.   STRUCTURE

The Crystal Structure of the Catalytic Domain of the NF-κB Inducing Kinase Reveals a Narrow but Flexible Active Site

(2012) Gladys de Leon-Boenig et al.   STRUCTURE

A Truncated Form of IKKα Is Responsible for Specific Nuclear IKK Activity in Colorectal Cancer

(2012) Pol Margalef et al.   Cell Reports

Deletion of cIAP1 and cIAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response

(2011) S. Gardam et al.   BLOOD

Mutations of NOTCH1 are an independent predictor of survival in chronic lymphocytic leukemia

(2011) D. Rossi et al.   BLOOD

Inhibitory kappa B kinases as targets for pharmacological regulation

(2011) Carly Gamble et al.   BRITISH JOURNAL OF PHARMACOLOGY

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Non-canonical NF-κB signaling activation and regulation: principles and perspectives

(2011) Bahram Razani et al.   IMMUNOLOGICAL REVIEWS

Analysis of the chronic lymphocytic leukemia coding genome: role ofNOTCH1mutational activation

(2011) Giulia Fabbri et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Crystal structure of inhibitor of κB kinase β

(2011) Guozhou Xu et al.   NATURE

Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

(2011) Xose S. Puente et al.   NATURE

Inflammation meets cancer, with NF-κB as the matchmaker

(2011) Yinon Ben-Neriah et al.   NATURE IMMUNOLOGY

Cleavage of NIK by the API2-MALT1 Fusion Oncoprotein Leads to Noncanonical NF- B Activation

(2011) S. Rosebeck et al.   SCIENCE

BAG3 is required for IKKα nuclear translocation and emergence of castration resistant prostate cancer

(2011) M Ammirante et al.   Cell Death & Disease

The lymph node microenvironment promotes B-cell receptor signaling, NF- B activation, and tumor proliferation in chronic lymphocytic leukemia

(2010) Y. Herishanu et al.   BLOOD

Classical and/or alternative NF- B pathway activation in multiple myeloma

(2010) Y. N. Demchenko et al.   BLOOD

Constitutive noncanonical NFκB signaling in pancreatic cancer cells

(2010) Catherine E. Wharry et al.   CANCER BIOLOGY & THERAPY

NF-κB in the regulation of epithelial homeostasis and inflammation

(2010) Andy Wullaert et al.   CELL RESEARCH

Non-canonical NF-κB signaling pathway

(2010) Shao-Cong Sun   CELL RESEARCH

NF-κB inducing kinase: A key regulator in the immune system and in cancer

(2010) Yee Mon Thu et al.   CYTOKINE & GROWTH FACTOR REVIEWS

Oncogenically active MYD88 mutations in human lymphoma

(2010) Vu N. Ngo et al.   NATURE

B-cell-derived lymphotoxin promotes castration-resistant prostate cancer

(2010) Massimo Ammirante et al.   NATURE

Telomere-independent Rap1 is an IKK adaptor and regulates NF-κB-dependent gene expression

(2010) Hsiangling Teo et al.   NATURE CELL BIOLOGY

IKKα and IKKβ Each Function to Regulate NF-κB Activation in the TNF-Induced/Canonical Pathway

(2010) Mazhar Adli et al.   PLoS One

Antigens in chronic lymphocytic leukemia—Implications for cell origin and leukemogenesis

(2010) Anders Rosén et al.   SEMINARS IN CANCER BIOLOGY

NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells

(2009) Takashi Nishina et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Structural insights into IKKβ inhibition by natural products staurosporine and quercetin

(2009) Carolina M. Avila et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

4-Phenyl-7-azaindoles as potent and selective IKK2 inhibitors

(2009) John Liddle et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Biologic sequelae of I B kinase (IKK) inhibition in multiple myeloma: therapeutic implications

(2009) T. Hideshima et al.   BLOOD

A Novel, Highly Selective, Tight Binding I B Kinase-2 (IKK-2) Inhibitor: A Tool to Correlate IKK-2 Activity to the Fate and Functions of the Components of the Nuclear Factor- B Pathway in Arthritis-Relevant Cells and Animal Models

(2009) G. Mbalaviele et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Notch-1 activates estrogen receptor-α-dependent transcription via IKKα in breast cancer cells

(2009) L Hao et al.   ONCOGENE

Geldanamycin inhibits tyrosine phosphorylation-dependent NF-κB activation

(2008) Julie Crèvecoeur et al.   BIOCHEMICAL PHARMACOLOGY

High-Affinity Interaction between IKKβ and NEMO

(2008) Yu-Chih Lo et al.   BIOCHEMISTRY

The NF- B subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

(2008) S. Hewamana et al.   BLOOD

Constitutively activated Notch signaling is involved in survival and apoptosis resistance of B-CLL cells

(2008) E. Rosati et al.   BLOOD

Cross-talk between Notch and the Estrogen Receptor in Breast Cancer Suggests Novel Therapeutic Approaches

(2008) P. Rizzo et al.   CANCER RESEARCH

Soluble and membrane levels of molecules involved in the interaction between clonal plasma cells and the immunological microenvironment in multiple myeloma and their association with the characteristics of the disease

(2008) Martin Perez-Andres et al.   INTERNATIONAL JOURNAL OF CANCER

Inhibition of Human Immunodeficiency Virus Type 1 Replication by Blocking I B Kinase with Noraristeromycin

(2008) K. Asamitsu et al.   JOURNAL OF BIOCHEMISTRY

Knowledge Based Prediction of Ligand Binding Modes and Rational Inhibitor Design for Kinase Drug Discovery

(2008) Arup K. Ghose et al.   JOURNAL OF MEDICINAL CHEMISTRY

Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling

(2008) Sivakumar Vallabhapurapu et al.   NATURE IMMUNOLOGY

Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK

(2008) Brian J Zarnegar et al.   NATURE IMMUNOLOGY

Is NF-κB a good target for cancer therapy? Hopes and pitfalls

(2008) Véronique Baud et al.   NATURE REVIEWS DRUG DISCOVERY

Oncogenic CARD11 Mutations in Human Diffuse Large B Cell Lymphoma

(2008) G. Lenz et al.   SCIENCE

Marine natural products as targeted modulators of the transcription factor NF-κB

(2007) Florence Folmer et al.   BIOCHEMICAL PHARMACOLOGY

Differential regulation of IKKα-mediated activation of IRF3/7 by NIK

(2007) Rui-Peng Wang et al.   MOLECULAR IMMUNOLOGY