TLR4

Synonyms

EC:3.2.2.6, TLR4, Toll Like Receptor 4, Toll-Like Receptor 4, HToll, Homolog Of Drosophila Toll, CD284 Antigen, ARMD10, CD284, TLR-4, TOLL, Toll Like Receptor 4 Protein,

Description

Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. It cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. It is also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni2+. Responses triggered by Ni2+ require non-conserved histidines and are, therefore, species-specific. Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. It binds electronegative LDL (LDL-) and mediates the cytokine release induced by LDL. Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor.

KO Status

F0

Drug Information

Launched drugs: 10
Drug in clinical trials: 1
Latest Research Phase:Approved

Drug Name

Code

Phase

Company

Indications

Clinical Trials

Ibudilast

AV-411, MN-166, KC-404

Approved

Diabetic Neuropathies, Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive, Pneumonia, Viral, Asthma, Neuralgia, Amyotrophic Lateral Sclerosis

EB-05

EB-05

Phase 3 Clinical

Edesa Biotech

Coronavirus Disease 2019 (COVID-19), Respiratory Distress Syndrome, Adult

PEPA-10

PEPA-10

Phase 2 Clinical

Immunovo

Neoplasms

DMT-210

DMT-200, DMT-210, DMT-220, SIG-990

Phase 2 Clinical

Signum Dermalogix

Rosacea, Dermatitis, Atopic

Glucopyranosyl lipid A

G-100, ID-G100

Phase 2 Clinical

Immune Design, Merck

Carcinoma, Merkel Cell, Influenza, Human, Sarcoma, Lymphoma, Non-Hodgkin

Anti-HERV-W humanized monoclonal antibodies (GeNeuro)

GNN-001, GNbAC-1, GENHP-01

Phase 2 Clinical

Geneuro

Multiple Sclerosis, Relapsing-Remitting, Diabetes Mellitus, Type 1, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Multiple Sclerosis

NI-0101

NI-0101

Phase 2 Clinical

Novimmune

Arthritis, Rheumatoid

Resatorvid

CLI-095, TAK-242

Phase 2 Clinical

Takeda Pharmaceutical Co Ltd

Shock, Septic, Sepsis, Acute-On-Chronic Liver Failure

SAR-439794

SAR-439794

Phase 1 Clinical

Sanofi

Food Hypersensitivity, Peanut Hypersensitivity

PET-lipid A

Phase 1 Clinical

Cascadian Therapeutics

Vaccination

GSK-1795091

1795091, GSK-1795091

Phase 1 Clinical

Glaxosmithkline Plc

Neoplasms

House dust mite allergy ultra-short course therapy (Allergy Therapeutics)

Phase 1 Clinical

Allergy Therapeutics

Rhinitis, Allergic

BL-1110

EDP-34, BL-1110

Pending

University Of Colorado At Boulder

Scleroderma, Systemic, Neuralgia

CRX-675

CRX-675

Pending

Glaxosmithkline Plc

Rhinitis, Allergic, Seasonal

ONT-10

ONT-10, BGLP-40, L-BGLP40

Discontinued

Cascadian Therapeutics

Ovarian Neoplasms, Breast Neoplasms

Eritoran Tetrasodium

B-1287, E-5564

Discontinued

University Of Texas Health Science Center At San Antonio

Shock, Septic, Leukemia, Sepsis, Systemic Inflammatory Response Syndrome

Defoslimod

OM-174, OM-174-DP

Discontinued

Vifor

Neoplasms

Monophosphoryl lipid A

MLA

Discontinued

Corixa

Immune System Diseases

E-5531

E-5531

Discontinued

Eisai Co Ltd

Shock, Septic, Gram-Negative Bacterial Infections

CS-4771

CS-4771

Discontinued

Daiichi Sankyo Co Ltd

Sepsis