SMAC mimetics and RIPK inhibitors as therapeutics for chronic inflammatory diseases

The transcription factor SP3 drives TNF-α expression in response to Smac mimetics

(2019) Shawn T. Beug et al.   Science Signaling

Death by inflammation: drug makers chase the master controller

(2019) Cormac Sheridan   NATURE BIOTECHNOLOGY

A NIK–SIX signalling axis controls inflammation by targeted silencing of non-canonical NF-κB

(2019) Zixu Liu et al.   NATURE

Inhibitor of Apoptosis Protein (IAP) Antagonists in Anticancer Agent Discovery: Current Status and Perspectives

(2019) Hui Cong et al.   JOURNAL OF MEDICINAL CHEMISTRY

Psoriasis Pathogenesis and Treatment

(2019) Adriana Rendon et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

The many faces of tumor necrosis factor signaling in the intestinal epithelium

(2019) M. Eugenia Delgado et al.   GENES AND IMMUNITY

RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases

(2019) Snahel Patel et al.   CELL DEATH AND DIFFERENTIATION

Challenges in IBD Research: Environmental Triggers

(2019) Shuk-Mei Ho et al.   INFLAMMATORY BOWEL DISEASES

Targeting RIPK1 for the treatment of human diseases

(2019) Alexei Degterev et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Cell Death and Inflammation – A Vital but Dangerous Liaison

(2019) Nieves Peltzer et al.   TRENDS IN IMMUNOLOGY

cIAP1/2 inhibition synergizes with TNF inhibition in autoimmunity by down-regulating IL-17A and inducing Tregs

(2019) Joanna Z. Kawalkowska et al.   Science Advances

TNFR1 and TNFR2 in the Control of the Life and Death Balance of Macrophages

(2019) Harald Wajant et al.   Frontiers in Cell and Developmental Biology

Keeping Cell Death in Check: Ubiquitylation-Dependent Control of TNFR1 and TLR Signaling

(2019) Laura Griewahn et al.   Frontiers in Cell and Developmental Biology

TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP

(2019) Janin Knop et al.   Cell Death & Disease

NOD Signaling and Cell Death

(2019) Valentin J. Heim et al.   Frontiers in Cell and Developmental Biology

The E3 ubiquitin ligases HOIP and cIAP1 are recruited to the TNFR2 signaling complex and mediate TNFR2-induced canonical NF-κB signaling

(2018) Alice Borghi et al.   BIOCHEMICAL PHARMACOLOGY

Smac mimetic induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFR1 signaling

(2018) Nadine Schmidt et al.   CANCER LETTERS

Genetics of immune-mediated inflammatory diseases

(2018) T. David et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Small molecule inhibitors reveal an indispensable scaffolding role of RIPK2 in NOD2 signaling

(2018) Matous Hrdinka et al.   EMBO JOURNAL

Etanercept for the treatment of rheumatoid arthritis

(2018) Sizheng Zhao et al.   Immunotherapy

Differentiated Macrophages Acquire a Pro-Inflammatory and Cell Death-Resistant Phenotype Due to Increasing XIAP and P38-mediated inhibition of RipK1

(2018) Dikchha Rijal et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TNF-α-Induced NOD2 and RIP2 Contribute to the Up-Regulation of Cytokines Induced by MDP in Monocytic THP-1 Cells

(2018) Xiaobin Chen et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

cIAP1/2–TRAF2–SHP-1–Src–MyD88 Complex Regulates Lipopolysaccharide-Induced IL-27 Production through NF-κB Activation in Human Macrophages

(2018) Aurelia Busca et al.   JOURNAL OF IMMUNOLOGY

Identification and Characterization of Novel Receptor-Interacting Serine/Threonine‐Protein Kinase 2 Inhibitors Using Structural Similarity Analysis

(2018) Mohamed Salla et al.   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

The inhibitor of apoptosis protein livin is upregulated in psoriasis vulgaris

(2018) H. Wang et al.   JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY

Disruption of XIAP-RIP2 Association Blocks NOD2-Mediated Inflammatory Signaling

(2018) Tatiana Goncharov et al.   MOLECULAR CELL

Regulatory T cells in autoimmune disease

(2018) Margarita Dominguez-Villar et al.   NATURE IMMUNOLOGY

Unique BIR domain sets determine inhibitor of apoptosis protein–driven cell death and NOD2 complex signal specificity

(2018) Steven M. Chirieleison et al.   Science Signaling

Necroptosis promotes cell-autonomous activation of proinflammatory cytokine gene expression

(2018) Kezhou Zhu et al.   Cell Death & Disease

IAPs Regulate Distinct Innate Immune Pathways to Co-ordinate the Response to Bacterial Peptidoglycans

(2018) Che A. Stafford et al.   Cell Reports

Unique BIR domain sets determine inhibitor of apoptosis protein–driven cell death and NOD2 complex signal specificity

(2018) Steven M. Chirieleison et al.   Science Signaling

Role of TNF–TNF Receptor 2 Signal in Regulatory T Cells and Its Therapeutic Implications

(2018) Sujuan Yang et al.   Frontiers in Immunology

Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses

(2018) Vinod Nadella et al.   Frontiers in Immunology

Structure-based design and molecular profiling of Smac-mimetics selective for cellular IAPs

(2018) Alessandro Corti et al.   FEBS Journal

A phase I study of a novel IAP inhibitor APG-1387 in patients with advanced solid tumors.

(2018) Ruihua Xu et al.   JOURNAL OF CLINICAL ONCOLOGY

RIP kinases as modulators of inflammation and immunity

(2018) Sudan He et al.   NATURE IMMUNOLOGY

Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death

(2018) Ricard Garcia-Carbonell et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Combination of a Latency-Reversing Agent With a Smac Mimetic Minimizes Secondary HIV-1 Infection in vitro

(2018) Shin-ichiro Hattori et al.   Frontiers in Microbiology

Biosimilars for Management of Crohn Disease

(2018) Ole Haagen Nielsen et al.   ANNALS OF INTERNAL MEDICINE

The safety of biological pharmacotherapy for the treatment of ulcerative colitis

(2017) Gionata Fiorino et al.   Expert Opinion On Drug Safety

The SMAC mimetic birinapant attenuates lipopolysaccharide-induced liver injury by inhibiting the tumor necrosis factor receptor–associated factor 3 degradation in Kupffer cells

(2017) Hongxiang Liu et al.   IMMUNOLOGY LETTERS

Expression Patterns of TNFα, MAdCAM1, and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease

(2017) Stephan R Vavricka et al.   Journal of Crohns & Colitis

Topical treatment of psoriasis: questionnaire results on topical therapy accessibility and influence of body surface area on usage

(2017) L. Iversen et al.   JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY

Crohn's disease

(2017) Joana Torres et al.   LANCET

Novel treatment strategies in rheumatoid arthritis

(2017) Gerd R Burmester et al.   LANCET

Ulcerative colitis

(2017) Ryan Ungaro et al.   LANCET

Therapeutic Potential of Targeting the Th17/Treg Axis in Autoimmune Disorders

(2017) Patrizia Fasching et al.   MOLECULES

Sphingosine-1-Phosphate Signaling in Inflammatory Bowel Disease

(2017) Ole Haagen Nielsen et al.   TRENDS IN MOLECULAR MEDICINE

Novel Targeted Therapies for Inflammatory Bowel Disease

(2017) Mehmet Coskun et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Identification of Potent and Selective RIPK2 Inhibitors for the Treatment of Inflammatory Diseases

(2017) Xiaohui He et al.   ACS Medicinal Chemistry Letters

RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome

(2017) Yingying Zhang et al.   Nature Communications

XIAP Loss Triggers RIPK3- and Caspase-8-Driven IL-1β Activation and Cell Death as a Consequence of TLR-MyD88-Induced cIAP1-TRAF2 Degradation

(2017) Kate E. Lawlor et al.   Cell Reports

The Safety and Immunogenicity of Live Zoster Vaccination in Patients With Rheumatoid Arthritis Before Starting Tofacitinib: A Randomized Phase II Trial

(2017) Kevin L. Winthrop et al.   Arthritis & Rheumatology

Role of Gut Microbiota in Rheumatoid Arthritis

(2017) Yuichi Maeda et al.   Journal of Clinical Medicine

Phase I study evaluating the safety, tolerability, and pharmacokinetics (PK) of HGS1029, a small-molecule inhibitor of apoptosis protein (IAP), in patients (pts) with advanced solid tumors.

(2017) S. G. Eckhardt et al.   JOURNAL OF CLINICAL ONCOLOGY

Crohn’s Disease Activity and Concomitant Immunosuppressants Affect the Risk of Serious and Opportunistic Infections in Patients Treated With Adalimumab

(2016) Mark T Osterman et al.   AMERICAN JOURNAL OF GASTROENTEROLOGY

Cellular and molecular regulation of innate inflammatory responses

(2016) Juan Liu et al.   Cellular & Molecular Immunology

A Phase I Dose-Escalation Study Evaluating the Safety Tolerability and Pharmacokinetics of CUDC-427, a Potent, Oral, Monovalent IAP Antagonist, in Patients with Refractory Solid Tumors

(2016) A. W. Tolcher et al.   CLINICAL CANCER RESEARCH

How genetic testing can lead to targeted management of XIAP deficiency–related inflammatory bowel disease

(2016) Ole Haagen Nielsen et al.   GENETICS IN MEDICINE

Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis

(2016) Milda Naciute et al.   JOURNAL OF GENERAL VIROLOGY

MicroRNA-17 Suppresses TNF-α Signaling by Interfering with TRAF2 and cIAP2 Association in Rheumatoid Arthritis Synovial Fibroblasts

(2016) Nahid Akhtar et al.   JOURNAL OF IMMUNOLOGY

IAP antagonists induce anti-tumor immunity in multiple myeloma

(2016) Marta Chesi et al.   NATURE MEDICINE

Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

(2016) Duncan E. Scott et al.   NATURE REVIEWS DRUG DISCOVERY

Mechanisms behind efficacy of tumor necrosis factor inhibitors in inflammatory bowel diseases

(2016) Caroline Meyer Olesen et al.   PHARMACOLOGY & THERAPEUTICS

The cybernetics of TNF: Old views and newer ones

(2016) David Wallach   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

Targeting JAK/STAT Signaling to Prevent Rejection After Kidney Transplantation

(2016) Carla C. Baan et al.   TRANSPLANTATION

Activation of TNFR2 sensitizes macrophages for TNFR1-mediated necroptosis

(2016) Daniela Siegmund et al.   Cell Death & Disease

Cellular inhibitor of apoptosis protein 2 controls human colonic epithelial restitution, migration, and Rac1 activation

(2015) Jakob Benedict Seidelin et al.   AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY

Pharmacodynamic markers and clinical results from the phase 2 study of the SMAC mimetic birinapant in women with relapsed platinum-resistant or -refractory epithelial ovarian cancer

(2015) Anne M. Noonan et al.   CANCER

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study

(2015) Herbert I. Hurwitz et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Inflammatory Signaling by NOD-RIPK2 Is Inhibited by Clinically Relevant Type II Kinase Inhibitors

(2015) Peter Canning et al.   CHEMISTRY & BIOLOGY

Promises and Challenges of Smac Mimetics as Cancer Therapeutics

(2015) S. Fulda   CLINICAL CANCER RESEARCH

Transmembrane TNF–TNFR2 Impairs Th17 Differentiation by PromotingIl2Expression

(2015) Patrick G. Miller et al.   JOURNAL OF IMMUNOLOGY

A Phase I Study of the SMAC-Mimetic Birinapant in Adults with Refractory Solid Tumors or Lymphoma

(2015) R. K. Amaravadi et al.   MOLECULAR CANCER THERAPEUTICS

The diverse role of RIP kinases in necroptosis and inflammation

(2015) John Silke et al.   NATURE IMMUNOLOGY

Targeting the IL-17–TH17 pathway

(2015) Hilary S. Bartlett et al.   NATURE REVIEWS DRUG DISCOVERY

Effects of physiological and synthetic IAP antagonism on c-IAP-dependent signaling

(2015) A J Kocab et al.   ONCOGENE

Expression and activity ofNOD1andNOD2/RIPK2signalling in mononuclear cells from patients with rheumatoid arthritis

(2015) RFO Franca et al.   SCANDINAVIAN JOURNAL OF RHEUMATOLOGY

XIAP deficiency syndrome in humans

(2015) Sylvain Latour et al.   SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY

A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production

(2015) Ueli Nachbur et al.   Nature Communications

Polyubiquitination of Transforming Growth Factor β-activated Kinase 1 (TAK1) at Lysine 562 Residue Regulates TLR4-mediated JNK and p38 MAPK Activation

(2015) I-Ting Chen et al.   Scientific Reports

RIP kinases: key decision makers in cell death and innate immunity

(2014) F Humphries et al.   CELL DEATH AND DIFFERENTIATION

Cellular Inhibitor of Apoptosis Protein cIAP2 Protects against Pulmonary Tissue Necrosis during Influenza Virus Infection to Promote Host Survival

(2014) Ian Gaël Rodrigue-Gervais et al.   Cell Host & Microbe

Characterization of Crohn disease in X-linked inhibitor of apoptosis–deficient male patients and female symptomatic carriers

(2014) Claire Aguilar et al.   JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

In VivoInhibition of RIPK2 Kinase Alleviates Inflammatory Disease

(2014) Justine T. Tigno-Aranjuez et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Phase I Dose-Escalation Study of LCL161, an Oral Inhibitor of Apoptosis Proteins Inhibitor, in Patients With Advanced Solid Tumors

(2014) Jeffrey R. Infante et al.   JOURNAL OF CLINICAL ONCOLOGY

Smac mimetics and innate immune stimuli synergize to promote tumor death

(2014) Shawn T Beug et al.   NATURE BIOTECHNOLOGY

Small-molecule SMAC mimetics as new cancer therapeutics

(2014) Longchuan Bai et al.   PHARMACOLOGY & THERAPEUTICS

The Neutrophil NLRC4 Inflammasome Selectively Promotes IL-1β Maturation without Pyroptosis during Acute Salmonella Challenge

(2014) Kaiwen W. Chen et al.   Cell Reports

XIAP Restricts TNF- and RIP3-Dependent Cell Death and Inflammasome Activation

(2014) Monica Yabal et al.   Cell Reports

Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation

(2013) Ryodai Shindo et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Toll-like Receptor 3-mediated Necrosis via TRIF, RIP3, and MLKL

(2013) William J. Kaiser et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Recurrent Hepatocellular Carcinoma: It's the Virus!

(2013) W. Ray Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and Inflammation

(2013) J. Silke et al.   Cold Spring Harbor Perspectives in Biology

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

(2013) Siqi Liu et al.   eLife

cIAP1 and cIAP2 limit macrophage necroptosis by inhibiting Rip1 and Rip3 activation

(2012) S McComb et al.   CELL DEATH AND DIFFERENTIATION

Apoptosis, necrosis and necroptosis: cell death regulation in the intestinal epithelium

(2012) Claudia Günther et al.   GUT

Inhibitor of Apoptosis Proteins Limit RIP3 Kinase-Dependent Interleukin-1 Activation

(2012) James E. Vince et al.   IMMUNITY

Critical Role for Antiapoptotic Bcl-xL and Mcl-1 in Human Macrophage Survival and Cellular IAP1/2 (cIAP1/2) in Resistance to HIV-Vpr-induced Apoptosis

(2012) Aurelia Busca et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Opposing Roles for TRAF1 in the AlternativeversusClassical NF-κB Pathway in T Cells

(2012) Ann J. McPherson et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Joint NOD2/RIPK2 Signaling Regulates IL-17 Axis and Contributes to the Development of Experimental Arthritis

(2012) S. M. Vieira et al.   JOURNAL OF IMMUNOLOGY

The Ubiquitin Ligase XIAP Recruits LUBAC for NOD2 Signaling in Inflammation and Innate Immunity

(2012) Rune Busk Damgaard et al.   MOLECULAR CELL

Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease

(2012) Luke Jostins et al.   NATURE

Cellular Inhibitors of Apoptosis Are Global Regulators of NF- B and MAPK Activation by Members of the TNF Family of Receptors

(2012) E. Varfolomeev et al.   Science Signaling

Inhibitor of Apoptosis Proteins as Novel Targets in Inflammatory Processes

(2011) Bettina A. Mayer et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

Smac Mimetics Activate the E3 Ligase Activity of cIAP1 Protein by Promoting RING Domain Dimerization

(2011) Rebecca Feltham et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

CpG Protects Human Monocytic Cells against HIV-Vpr-Induced Apoptosis by Cellular Inhibitor of Apoptosis-2 through the Calcium-Activated JNK Pathway in a TLR9-Independent Manner

(2011) M. Saxena et al.   JOURNAL OF IMMUNOLOGY

Use of biological molecules in the treatment of inflammatory bowel disease

(2011) O. H. Nielsen et al.   JOURNAL OF INTERNAL MEDICINE

cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms

(2011) Maria Feoktistova et al.   MOLECULAR CELL

The Ripoptosome, a Signaling Platform that Assembles in Response to Genotoxic Stress and Loss of IAPs

(2011) Tencho Tenev et al.   MOLECULAR CELL

Antagonists Induce a Conformational Change in cIAP1 That Promotes Autoubiquitination

(2011) E. C. Dueber et al.   SCIENCE

MAP kinases in inflammatory bowel disease

(2010) Mehmet Coskun et al.   CLINICA CHIMICA ACTA

Virus-triggered Ubiquitination of TRAF3/6 by cIAP1/2 Is Essential for Induction of Interferon-β (IFN-β) and Cellular Antiviral Response

(2010) Ai-Ping Mao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cellular Inhibitors of Apoptosis cIAP1 and cIAP2 Are Required for Innate Immunity Signaling by the Pattern Recognition Receptors NOD1 and NOD2

(2009) Mathieu J.M. Bertrand et al.   IMMUNITY

Recruitment of the Linear Ubiquitin Chain Assembly Complex Stabilizes the TNF-R1 Signaling Complex and Is Required for TNF-Mediated Gene Induction

(2009) Tobias L. Haas et al.   MOLECULAR CELL

Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokines

(2009) Ping-Hui Tseng et al.   NATURE IMMUNOLOGY

Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production

(2009) Mikyoung Chang et al.   NATURE IMMUNOLOGY

XIAP mediates NOD signaling via interaction with RIP2

(2009) A. Krieg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

SM-164: A Novel, Bivalent Smac Mimetic That Induces Apoptosis and Tumor Regression by Concurrent Removal of the Blockade of cIAP-1/2 and XIAP

(2008) J. Lu et al.   CANCER RESEARCH

TNF-α Induces Two Distinct Caspase-8 Activation Pathways

(2008) Lai Wang et al.   CELL

Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics

(2008) A. C. Mita et al.   CLINICAL CANCER RESEARCH

Identification of RIP1 kinase as a specific cellular target of necrostatins

(2008) Alexei Degterev et al.   Nature Chemical Biology

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

IAP-targeted therapies for cancer

(2008) E C LaCasse et al.   ONCOGENE

Both cIAP1 and cIAP2 regulate TNF -mediated NF- B activation

(2008) D. J. Mahoney et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA