Discovery and Development of Toll-Like Receptor 4 (TLR4) Antagonists: A New Paradigm for Treating Sepsis and Other Diseases

Innate Immune Recognition

2002 • 8,157 citations

A human homologue of the Drosophila Toll protein signals activation of adaptive immunity

1997 • 5,522 citations

CD14, a Receptor for Complexes of Lipopolysaccharide (LPS) and LPS Binding Protein

1990 • 4,041 citations

The Pathophysiology and Treatment of Sepsis

2003 • 4,027 citations

The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling

2007 • 2,524 citations

LPS induction of gene expression in human monocytes

2001 • 2,276 citations

MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4

1999 • 2,188 citations

Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction

1999 • 1,905 citations

Negative regulation of Toll-like receptor-mediated immune responses

2005 • 1,487 citations

The Extra Domain A of Fibronectin Activates Toll-like Receptor 4

2001 • 1,200 citations

Septic Shock in Humans

1990 • 1,170 citations

Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran

2007 • 1,082 citations

The Toll gene of drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein

1988 • 1,077 citations

Fibrinogen Stimulates Macrophage Chemokine Secretion Through Toll-Like Receptor 4

2001 • 947 citations

High mobility group box 1 protein interacts with multiple Toll-like receptors

2005 • 905 citations

Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation.

2002 • 843 citations

Epidemiology of sepsis: An update

2001 • 823 citations

Expression of Toll-Like Receptors in Human Atherosclerotic Lesions

2002 • 669 citations

CD14 is required for MyD88-independent LPS signaling

2005 • 645 citations

Structure and Function of Toll Receptors and Their Ligands

2007 • 634 citations

Toll-like receptors: From the discovery of NFκB to new insights into transcriptional regulations in innate immunity

2006 • 575 citations

Relationship between Plasma Levels of Lipopolysaccharide (LPS) and LPS‐Binding Protein in Patients with Severe Sepsis and Septic Shock

1999 • 575 citations

Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation

2002 • 460 citations

Hepatic Ischemia/Reperfusion Injury Involves Functional TLR4 Signaling in Nonparenchymal Cells

2005 • 356 citations

Signaling Danger

2004 • 352 citations

A Novel Cyclohexene Derivative, Ethyl (6R)-6-[N-(2-Chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242), Selectively Inhibits Toll-Like Receptor 4-Mediated Cytokine Production through Suppression of Intracellular Signaling

2005 • 340 citations

E5531, a Pure Endotoxin Antagonist of High Potency

1995 • 322 citations

Innate immune activation in neutrophilic asthma and bronchiectasis

2006 • 320 citations

Cytokine regulation of liver injury and repair

2000 • 296 citations

Use of the Gram stain in microbiology

2001 • 291 citations

Inhibition of Endotoxin Response by E5564, a Novel Toll-Like Receptor 4-Directed Endotoxin Antagonist

2002 • 290 citations

Structural biology of the LPS recognition

2007 • 284 citations

TAK-242 selectively suppresses Toll-like receptor 4-signaling mediated by the intracellular domain

2008 • 282 citations

Chlamydia pneumoniae and Chlamydial Heat Shock Protein 60 Stimulate Proliferation of Human Vascular Smooth Muscle Cells via Toll-Like Receptor 4 and p44/p42 Mitogen-Activated Protein Kinase Activation

2001 • 278 citations

Inhibition of Toll-like Receptor 4 With Eritoran Attenuates Myocardial Ischemia-Reperfusion Injury

2006 • 274 citations

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

2004 • 237 citations

MyD88-deficient mice develop severe intestinal inflammation in dextran sodium sulfate colitis

2005 • 232 citations

A Synthetic TLR4 Antagonist Has Anti-Inflammatory Effects in Two Murine Models of Inflammatory Bowel Disease

2005 • 217 citations

Lipoproteins in inflammation and sepsis. II. Clinical aspects

2006 • 178 citations

Therapeutic effects of TAK-242, a novel selective Toll-like receptor 4 signal transduction inhibitor, in mouse endotoxin shock model

2007 • 174 citations

Statins Decrease Toll-Like Receptor 4 Expression and Downstream Signaling in Human CD14 ⁺ Monocytes

2005 • 164 citations

Protection against Myocardial Ischemia/Reperfusion Injury in TLR4-Deficient Mice Is Mediated through a Phosphoinositide 3-Kinase-Dependent Mechanism

2007 • 156 citations

Blocking of Responses to Endotoxin by E5564 in Healthy Volunteers with Experimental Endotoxemia

2003 • 149 citations

The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases

2007 • 148 citations

Subversion of the innate immune system by a retrovirus

2003 • 141 citations

The extra domain A of fibronectin stimulates murine mast cells via Toll-like receptor 4

2007 • 139 citations

Structure and function of Toll-like receptor proteins

2000 • 137 citations

Toll receptors: an expanding role in our understanding of human disease

2000 • 101 citations

Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease

2006 • 96 citations

Toll-like receptor expression in chronic hepatitis C: Correlation with pro-inflammatory cytokine levels and liver injury

2006 • 96 citations

Targeting Bacterial Endotoxin

2007 • 94 citations

Inhibition of Endotoxin Response by Synthetic TLR4 Antagonists

2004 • 90 citations

A Novel Synthetic Acyclic Lipid A-like Agonist Activates Cells via the Lipopolysaccharide/Toll-like Receptor 4 Signaling Pathway

2001 • 84 citations

Drotrecogin alfa (activated) (recombinant human activated protein C) for the treatment of severe sepsis

2003 • 83 citations

Synthetic TLR4-active Glycolipids as Vaccine Adjuvants and Stand-alone Immunotherapeutics

2008 • 79 citations

Toll-Like Receptor 4 Mediates the Early Inflammatory Response After Cold Ischemia/Reperfusion

2007 • 78 citations

Lipopolysaccharide as a Target for the Development of Novel Therapeutics in Gram-Negative Bacteria

2001 • 76 citations

Safety, Pharmacokinetics, Pharmacodynamics, and Plasma Lipoprotein Distribution of Eritoran (E5564) during Continuous Intravenous Infusion into Healthy Volunteers

2004 • 72 citations

A Phase II, Double-Blind, Placebo-Controlled, Ascending-Dose Study of Eritoran (E5564), a Lipid A Antagonist, in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass

2007 • 68 citations

Synthesis and biological evaluation of a new class of vaccine adjuvants: aminoalkyl glucosaminide 4-phosphates (AGPs)

1999 • 67 citations

‘Toll’ Gates for Future Immunotherapy

2006 • 65 citations

Effects of ketamine on levels of cytokines, NF-κB and TLRs in rat intestine during CLP-induced sepsis

2007 • 64 citations

Lipopolysaccharide induces expression of genes encoding pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human cervical smooth-muscle cells

2000 • 62 citations

Safety, Pharmacokinetics, and Pharmacodynamics of E5564, a Lipid A Antagonist, during an Ascending Single-Dose Clinical Study

2003 • 54 citations

E5564 (Eritoran) inhibits lipopolysaccharide-induced cytokine production in human blood monocytes

2006 • 52 citations

Use of the Gram stain in microbiology

2001 • 50 citations

Role of Toll-like receptor 4 for the pathogenesis of acute lung injury in Gram-negative sepsis

2006 • 50 citations

The inflammatory response to ischemic acute kidney injury: a result of the ‘right stuff’ in the ‘wrong place’?

2007 • 49 citations

Critical role of Toll-like receptors and the common TLR adaptor, MyD88, in induction of granulomas and liver injury

2006 • 41 citations

Response of human macrophage‐like cells to stimulation by Fusobacterium nucleatum ssp. nucleatum lipopolysaccharide

2006 • 39 citations

Consequences of Interaction of a Lipophilic Endotoxin Antagonist with Plasma Lipoproteins

2000 • 36 citations

Pathogen‐specific TLR signaling in mucosa: Mutual contribution of microbial TLR agonists and virulence factors

2006 • 34 citations

Lipopolysaccharide regulates toll‐like receptor 4 expression in human aortic smooth muscle cells

2007 • 29 citations

Review article: inflammatory bowel disease and genetics

2007 • 29 citations

Lipoprotein Distribution of a Novel Endotoxin Antagonist, E5531, in Plasma from Human Subjects with Various Lipid Levels

1999 • 24 citations

Endotoxin Tolerance Inhibits Lipopolysaccharide‐Initiated Acute Pulmonary Inflammation and Lung Injury in Rats by the Mechanism of Nuclear Factor‐κB

2003 • 21 citations

Association of the Endotoxin Antagonist E5564 with High-Density Lipoproteins In Vitro: Dependence on Low-Density and Triglyceride-Rich Lipoprotein Concentrations

2003 • 15 citations

Anti-endotoxin activity of a novel synthetic lipid A analog.

1995 • 13 citations

LPS binding protein does not participate in the pharmacokinetics of E5564

2004 • 7 citations