EC:, 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


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

F1 (+/-)

Drug Information

Launched drug: 1
Drugs in clinical trials: 10
Latest Research Phase: Approved

Drug Name





Clinical Trials


AV-411, KC-404, MN-166


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



Phase 3 Clinical

Edesa Biotech

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



Phase 2 Clinical


Arthritis, Rheumatoid


Phase 2 Clinical

aptaTargets SL


Glucopyranosyl lipid A

G-100, ID-G100

Phase 2 Clinical

Immune Design, Merck

Carcinoma, Merkel Cell, Influenza A virus infections, Sarcoma, Lymphoma, Non-Hodgkin



Phase 2 Clinical




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

Phase 2 Clinical

Signum Dermalogix

Rosacea, Dermatitis, Atopic

Anti-HERV-W humanized monoclonal antibodies (GeNeuro)

GNN-001, GNbAC-1, GENHP-01

Phase 2 Clinical


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


CLI-095, TAK-242

Phase 2 Clinical

Takeda Pharmaceutical Co Ltd

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

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

Phase 1 Clinical

Allergy Therapeutics

Rhinitis, Allergic





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