resatorvid (TAK-242) / Takeda, Akaza Bioscience - LARVOL DELTA

Zinc gluconate attenuates oxaliplatin-induced pulmonary injury via suppressing the TLR4/NF-κB signaling. (PubMed, Biochem Pharmacol) - "Pharmacological inhibition of TLR4 with resatorvid (Tak242) effectively reversed these effects, further confirming the central role of this pathway. Collectively, these findings demonstrate that OXA induces pulmonary injury via TLR4 /NF-κB-dependent inflammatory and fibrosis, and that ZG exerts protective effects by suppressing this signaling. Our study identifies as a promising therapeutic target and highlights ZG as a potential adjunctive strategy for preventing OXA-associated pulmonary toxicity."

Journal • Fibrosis • Immunology • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • MYD88 • TLR4

Large-scale organoid-derived cyst cultures as a drug discovery platform for polycystic kidney disease. (PubMed, Kidney Int) - "We have developed a scalable method to generate cystic UB organoids, providing a simple and efficient platform for ADPKD drug discovery."

IO biomarker • Journal • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • TLR4

A-TANGO Phase 2 Study (clinicaltrials.gov) - P2 | N=78 | Recruiting | Sponsor: Yaqrit Ltd | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Feb 2026 ➔ Aug 2028

Enrollment open • Trial completion date • Trial primary completion date • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure

mTOR/Autophagy//NF-κB Axis Drives Benzalkonium Chloride-Induced Inflammatory Response in Corneal Epithelial Cells. (PubMed, J Ocul Pharmacol Ther) - "These results unveil mTOR as a therapeutic target for mitigating BAK-induced corneal damage, thereby proposing mTOR suppression or autophagic activation as viable interventions for BAK-associated ocular surface disorders. Particularly at lower concentration (0.001%) and shorter exposure (15 min) of BAK."

Journal • Corneal Abrasion • Inflammation • Ophthalmology • IL1B • IL6 • MYD88 • TLR4

Emodin attenuates influenza virus induced acute lung injury by modulating lung TLR4/MyD88/NF-κB and ILC3/IL-17A activation in a gut microbiota-dependent pattern (ERS 2026) - "TAK-242 blocked ILC3 activation, whereas LPS counteracted emodin's regulatory impact on ILC3/IL-17A. Emodin reduced gut microbiota derived LPS to inhibit the lung TLR4/MyD88/NF-κB pathway and subsequently suppressed ILC3/IL-17A axis, alleviated lung inflammation and tissue damage induced by influenza virus."

Gut Microbiota • Acute Lung Injury • Infectious Disease • Inflammation • Influenza • Pneumonia • Respiratory Diseases • IL17A • IL1B • MYD88 • OCLN • TJP1 • TLR4

Impact of extraction techniques on the structural features and immunomodulatory activity of polysaccharides from Cremastra appendiculata. (PubMed, Int J Biol Macromol) - "TAK-242 attenuated all three ACE-P-induced responses, C29 had no significant effect under the conditions tested, and BAY 11-7082 reduced NO and IL-6 but not TNF-α, supporting TLR4-associated activation and differential downstream regulation of these mediators. Exploratory across-fraction correlations suggested that higher activity co-occurred with higher carbohydrate content and lower molecular weight and O-acetylation, although UAE-P showed that low molecular weight alone was insufficient. These findings demonstrate extraction-dependent variation in CAP structure and macrophage-stimulatory activity and identify ACE-P as a candidate for further mechanistic and in vivo evaluation."

Journal • Oncology • IL6 • TLR4 • TNFA

Zonisamide attenuates morphine tolerance in association with reduced spinal TLR4/p38 MAPK signaling. (PubMed, Front Pharmacol) - "Pharmacological inhibition of TLR4 with TAK-242 was used to verify the involvement of TLR4 signaling. These findings indicate that zonisamide attenuates morphine tolerance in association with reduced spinal TLR4/p38 MAPK signaling and neuroinflammation. This study provides a mechanistic rationale for repurposing zonisamide as an adjunct therapy to improve long-term pain management and mitigate opioid-related adverse effects."

IO biomarker • Journal • Inflammation • Oncology • Pain • IL1B • IL6 • TLR4 • TNFA

Ribes fasciculatum Leaf Water Extract Enhances Macrophage Immune Responses via TLR4-Mediated JNK and NF-κB Activation in RAW264.7 Cells. (PubMed, J Microbiol Biotechnol) - "The immunostimulatory effects of RFL-DW20 were strongly inhibited by TAK-242, SP600125, and BAY 11-7082, suggesting the involvement of TLR4, JNK, and NF-κB signaling. Ethanol precipitation further enriched its NO-inducing activity. These findings suggest that RFL-DW20 activates macrophages through the TLR4/JNK/NF-κB signaling axis and may serve as a natural immune-stimulating material."

Journal • IL1B • IL6 • NFKBIA • PTGS2 • TLR4 • TNFA

Electroacupuncture Attenuates Neuroinflammation in PCPA-Induced Insomnia Rats by Suppressing the TLR4/MyD88/NF-κB p65 Pathway and M1 Microglial Activation. (PubMed, Neuropsychiatr Dis Treat) - "This animal study investigated whether EA attenuates hypothalamic neuroinflammation in para-chlorophenylalanine (PCPA)-induced insomnia rats by suppressing the TLR4/MyD88/NF-κB p65 pathway and M1 microglial activation, using TAK-242 (HY-11109), a selective TLR4 inhibitor, as a positive control...Electroacupuncture effectively improved sleep disturbances in PCPA-induced insomnia rats. The underlying mechanism may be associated with inhibition of the TLR4/MyD88/NF-κB p65 signaling pathway, suppression of M1 microglial activation, and downregulation of pro-inflammatory cytokines, thereby partly alleviating hypothalamic neuroinflammation."

Journal • Preclinical • CNS Disorders • Inflammation • Insomnia • Oncology • Sleep Disorder • CD86 • IL6 • MYD88 • TLR4 • TNFA

Direct toll-like receptor 4 inhibition in Alzheimer's disease models: a focused scoping review of inflammatory, amyloid-handling, and functional outcomes. (PubMed, Front Aging Neurosci) - "Original AD- or Aβ-related animal, cellular, and ex vivo studies were eligible when they directly inhibited, antagonized, or genetically suppressed TLR4 signaling using pharmacological approaches, including TAK-242/CLI-095/resatorvid, IAXO-101, RSLA, or related TLR4-targeting strategies, or genetic approaches such as TLR4 siRNA, knockdown, knockout, or loss-of-function mutation...APOE genotype, sex, treatment window, model system, Aβ species, and intervention type appeared to modify the direction of downstream effects. Toll-like receptor 4 suppression relatively consistently attenuated inflammatory readouts, whereas amyloid-related and functional outcomes remained heterogeneous, supporting an exploratory, hypothesis-generating model of context-dependent inflammatory-amyloid-functional dissociation rather than a uniform therapeutic benefit."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • APOE • NLRP3 • TLR4

CIRP Promotes Redox-Inflammatory Endothelial Injury in High-Fat Diet-Fed ApoE-/- Mice and HUVECs: Involvement of TLR4/SIRT6 Signaling. (PubMed, Antioxidants (Basel)) - "Accordingly, pharmacological TLR4 inhibition with TAK-242 attenuated CIRP-associated endothelial injury and partially restored SIRT6 expression and protein stability...The results are also consistent with the possible involvement of TLR4-/SIRT6-related signaling. These observations should be interpreted cautiously because of the relatively high CIRP concentration used in vitro, the cross-context transcriptomic comparison, and the small clinical cohort."

Journal • Preclinical • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure • Inflammation • APOE • GPX4 • NOS3 • SIRT6 • TLR4

The Characterization of a New AG-II-like Glycoprotein from Cynanchum thesioides (Freyn) K. Schum and Its Immunostimulatory Activity Through Activation of TLR4/9-Mediated MAPK/NF-κB Signaling Pathways. (PubMed, Curr Issues Mol Biol) - "Inhibitor assays showed that Toll-like receptor 4 (TLR4, TAK-242) and Toll-like receptor 9 (TLR9, E6446) antagonists markedly reduced CTSP-W2-induced TNF-α, IL-6, and NO in a dose-dependent manner, whereas Toll-like receptor 2 (TLR2) inhibition (C29) unexpectedly upregulated these mediators...Furthermore, Molecular docking analysis further indicated that CTSP-W2 forms extremely strong hydrogen-bonding and hydrophobic interactions with TLR4 through its galactose chains. This study elucidates the immunoregulatory mechanism of CTSP-W2 and establishes a molecular basis for arabinogalactan proteins as potential natural immunomodulators."

IO biomarker • Journal • Oncology • IL6 • NFKBIA • TLR2 • TLR4 • TNFA

Toll-Like Receptors in the Mechanism of Hexabromocyclododecane-Induced Production of Pro-Inflammatory Cytokines. (PubMed, J Appl Toxicol) - "PBMCs were pretreated with selective inhibitors targeting TLR1/2 (CUCPT 22), TLR2 (C29), TLR3 (CUCPT 4a), TLR4 (TAK-242), TLR8 (CUCPT 9a), and MyD88 (TJ-M2010-5), followed by exposure to HBCD (1-5 μM)...Inhibition of the TLR-associated adaptor protein MyD88 significantly attenuated HBCD-induced IL-1β and IL-6 production, whereas TNF-α production was not consistently affected. These results further elucidate the mechanism by which HBCD leads to elevation of pro-inflammatory cytokine production by human immune cells."

Journal • Cardiovascular • Immunology • Inflammation • Oncology • IL1B • IL6 • MYD88 • TLR2 • TLR3 • TLR4 • TLR8 • TNFA

Jiu-Wei-Yong-An decoction alleviates atopic dermatitis by suppressing TLR4/MyD88/NF-κB signaling pathway. (PubMed, J Ethnopharmacol) - "JWYA ameliorates AD through multi-component, multi-target modulation of the TLR4/MyD88/NF-κB inflammatory axis. Phylliroside and Suspenoidside B are key bioactive substances that directly bind TLR4/MyD88/NF-κB to inhibit NF-κB hyperactivation, relieving AD-related inflammation. This study provides experimental basis for JWYA's clinical application and subsequent monomer drug development."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IFNG • MYD88 • TLR4 • TNFA

Nogo-B deletion mitigates mitochondrial dynamics imbalance in cerebral ischemia/reperfusion injury via the TLR4/ERK pathway. (PubMed, Exp Neurol) - "Nogo-B deletion has a direct protective effect on neurons after cerebral ischemia-reperfusion injury. The mechanism may be related to Nogo-B reducing the expression of TLR4 on the cell membrane through some indirect action, thereby inhibiting the TLR4/ERK pathway and regulating mitochondrial dynamic imbalance."

Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Reperfusion Injury • MFN2

Berberine attenuates necrotizing enterocolitis-associated brain injury via the TLR4/MyD88/NF-κB/NLRP3 pathway (PubMed, Zhongguo Dang Dai Er Ke Za Zhi) - "BBR can alleviate brain injury in NEC model mice and improve long-term neurological outcomes dose-dependently. These effects likely involve preservation of BBB integrity and suppression of microglial activation via inhibition of the TLR4/MyD88/NF-κB/NLRP3 signaling pathway."

Journal • CNS Disorders • Gastrointestinal Disorder • Oncology • Vascular Neurology • CLDN5 • IL1B • IL6 • MYD88 • NLRP3 • OCLN • TJP1 • TLR4 • TNFA

Isoorientin attenuates aging-induced bone deterioration by suppressing M1-mediated TLR4-MAPK-NF-κB inflammatory signaling. (PubMed, Biogerontology) - "Isoorientin alleviates age-related bone loss by suppressing TLR4-mediated inflammation, reducing osteoclast activation, and restoring impaired osteogenesis. These findings identify isoorientin as a promising therapeutic candidate for age-associated osteoporosis."

IO biomarker • Journal • Inflammation • Osteoporosis • Rheumatology • TLR4

Electroacupuncture alleviates articular chondrocyte apoptosis in rats with knee osteoarthritis by regulating the TLR4/MyD88/NF-κB signaling pathway (PubMed, Nan Fang Yi Ke Da Xue Xue Bao) - "EA alleviates cartilage injury in KOA rats possibly by inhibiting HMGB1-mediated activation of TLR4/MyD88/NF‑κB signaling and NF‑κB p65 nuclear translocation to regulate Bcl-2/Bax balance and suppress mitochondria-dependent chondrocyte apoptosis."

IO biomarker • Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • BAX • BCL2 • CASP3 • HMGB1 • IL1B • MYD88 • RELA • TLR4 • TNFA

Phillyrin Alleviates Memory Impairment in D-Galactose-Induced Aged Mice by Suppressing Hippocampal Neuroinflammation via the TLR4/NF-κB Signaling Pathway. (PubMed, Food Sci Nutr) - "Moreover, PHI downregulated TLR4, p-IκBα, and p-NF-κB expression both in hippocampal tissue and HT22 cells, consistent with the effects of the TLR4 inhibitor TAK-242. These findings suggest that PHI exerts neuroprotective and anti-inflammatory effects via TLR4/NF-κB modulation, highlighting its potential as a dietary bioactive compound to support cognitive health during aging."

IO biomarker • Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • NFKBIA • TLR4

Role of the TLR4-NF-κB-FDX1 cuproptosis axis in mediating cognitive impairment associated with type 1 diabetes in children: an exploratory mechanistic study. (PubMed, Metab Brain Dis) - "Cells received TLR4 inhibitor TAK-242 or FDX1 knockdown...ChIP-qPCR confirmed that NF-κB bound directly to the FDX1 promoter to enhance its transcription. This study demonstrated for the first time that the TLR4-NF-κB-FDX1 cuproptosis axis plays a key pathological role in T1DM-related cognitive impairment, offering a new avenue for targeted therapy."

Journal • Alzheimer's Disease • Cognitive Disorders • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • DLAT • FDX1 • TLR4

Targeting TLR4 with ligustrazine and AT1R with telmisartan ameliorates diabetic kidney disease. (PubMed, Transl Res) - "In-vitro, high-glucose-rh-TGF-β1-stimulated NRK-52E cells were treated with ligustrazine-50 µM, telmisartan-10µM, and their combination, alongside TAK-242-100nM (TLR4 inhibitor control), and cell samples were processed for cell viability, morphology, immunocytochemistry and immunoblotting. Collectively, the combination therapy showed greater anti-inflammatory and antifibrotic potential than monotherapies. These findings indicate that ligustrazine with telmisartan enhances renoprotection and allows a lower telmisartan dose, potentially reducing its side effects and improving overall therapeutic outcomes in DKD."

Journal • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Immunology • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • CTNNB1 • IL18 • IL1B • NLRP3 • TGFB1 • TLR4 • VIM

Growth Differentiation Factor 15 (GDF15) Protects Against Sepsis-Associated Acute Kidney Injury via Suppression of TLR4-MyD88-NF-κB Signaling and Ferroptosis. (PubMed, Biofactors) - "In HK-2 cells, GDF15 silencing aggravated LPS-induced loss of viability, apoptosis, cytokine release, oxidative stress, and ferroptosis markers, all reversed by TAK242. In conclusion, GDF15 is a stress-inducible renoprotective factor that suppresses TLR4 signaling, ferroptosis markers, and inflammation in SAKI, suggesting exogenous administration as a promising therapeutic strategy."

Journal • Acute Kidney Injury • Infectious Disease • Inflammation • Nephrology • Renal Disease • Septic Shock • ANXA5 • GDF15 • GPX4 • IL1B • IL6 • KIM1 • MYD88 • SLC7A11 • TLR4 • TNFA

PCSK9 Inhibitor Attenuates Platelet TLR4 in ACS and TLR4 Blockers Prevent PCSK9-Mediated Platelet Activation. (PubMed, Acta Cardiol Sin) - "Platelet-rich plasma from healthy volunteers (n = 5) was incubated with normal saline, PCSK9, PCSK9 + evolocumab, or PCSK9 + the TLR4 inhibitor resatorvid (TAK-242). The pro-aggregatory effects of PCSK9 on platelets were counteracted by TLR4 inhibition, indicating a mechanistic link between PCSK9 and TLR4 signaling in platelet activation. Co-localization of TLR4 and PCSK9 in MEG-01 cells supports a potential interaction between the two proteins."

IO biomarker • Journal • Acute Coronary Syndrome • Cardiovascular • Hematological Malignancies • Leukemia • Oncology • TLR4

A PTX3/TLR4 axis sustains SHH-Medulloblastoma growth and defines a new therapeutic vulnerability. (PubMed, Neuro Oncol) - "Our findings identify PTX3-TLR4 signaling as key oncogenic driver and a promising therapeutic vulnerability in SHH-MB. Targeting this pathway enhances the efficacy of standard therapy and represents a rationale for mechanism-based combination strategies."

Journal • Brain Cancer • Medulloblastoma • Oncology • Pediatrics • Solid Tumor • IRAK1 • PTX3 • TLR4

Combination of High-Fat Diet and Chronic Unpredictable Stress Synergistically Induces Osteoarthritis-Like Changes in Temporomandibular Joints in Rats. (PubMed, Mediators Inflamm) - "HFD and CUS could synergistically induce TMJOA-like changes, potentially by activating the TLR4/NF-κB/IL-1β inflammatory signaling pathway. Our findings suggest an important interplay between metabolic and psychological factors in the pathogenesis of TMJOA."

Journal • Preclinical • Immunology • Osteoarthritis • Pain • Rheumatology • IL1B • TLR4