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

MicroRNA Containing Exosomes Released from Stressed Islets Induce Beta-Cell Differentiation and Proliferation of Adult Islet Progenitor Cells (WTC 2025) - "Induction of cell cycle genes was enhanced by toll like receptor 4 (TLR4) inhibitor TAK242, dual-specificity tyrosine-regulated kinase (DYRK) inhibitors harmine and GNF4877, and small molecule differentiation inducer isoxazole 9 (ISX9)... Exosomes released by stressed islets turn on dedifferentiation, survival, and proliferation transcriptional profiles in IPCs by inhibition of TLR4 signaling and stimulation of the calcineurin/NFAT pathways. The results indicate potential use of exosomes for in vivo and in vitro biologics to expand islet progenitor cells for islet cell replacement therapy to prevent or reverse diabetes."

Clinical • IO biomarker • Diabetes • Metabolic Disorders • BCL2 • CCNA2 • FOXM1 • IFNG • IL1B • TNFA • TOP2A

Mechanisms of Pain Hypersensitivity in a Human Skin Inflammation Model (clinicaltrials.gov) - P1 | N=42 | Completed | Sponsor: Stefan Heber

New P1 trial • Dermatitis • Immunology • Inflammation • Pain

A-TANGO Phase 2 Study (clinicaltrials.gov) - P2 | N=78 | Not yet recruiting | Sponsor: Yaqrit Ltd | Initiation date: Mar 2025 ➔ Sep 2025

Trial initiation date • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure

Involvement of Microglia in Retinal Ganglion Cell Injury Induced by IOP Elevation in a Rat Ex Vivo Acute Glaucoma Model. (PubMed, Biomedicines) - "Effects of PLX5622, an agent that depletes microglia, were examined in morphology, apoptosis, and protein expression assays, while TAK-242, a TLR4 inhibitor, was examined against protein expression. These results indicate that pressure elevation induces proliferation of inflammatory microglia and promotes IL-1β production via activation of the TLR4-NLRP3 inflammasome cascade, resulting in RGC death. Pharmacological depletion of microglia with PLX5622 could be a potential neuroprotective approach to preserve RGCs from inflammatory cytokines in AAC eyes."

Journal • Preclinical • Glaucoma • Inflammation • Ophthalmology • IL1B • NLRP3 • TLR4

Maresin1 improves postoperative delirium-like behavior in mice with tibial fractures by inhibiting the TLR4/MyD88/NF-kB pathway. (PubMed, J Neuroimmunol) - "MaR1, whether used alone or in combination with TAK-242, demonstrates significant anti-inflammatory and neuroprotective effects in a POD mouse model, achieved likely through the inhibition of TLR4/MyD88/NF-kB activation. These findings suggest that targeting TLR4/MyD88/NF-kB inflammatory pathway may help prevent or mitigate POD in surgical patients."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Inflammation • Musculoskeletal Diseases • Orthopedics • GFAP • MYD88 • TLR4

Pan-Cancer Analyses of Necroptosis, Pyroptosis and Ferroptosis Related Genes Reveal TLR4 as A Potential Therapeutic Target. (PubMed, J Cell Mol Med) - "Moreover, treatment with the TLR4 inhibitor TAK-242 was shown to inhibit cell proliferation and migration in PANC-1 and SW1990 cell lines. These findings underscore the potential of NPF-related pathways as prognostic biomarkers and support TAK-242 as a promising therapeutic candidate for cancer treatment."

Biomarker • Journal • Pan tumor • Oncology • TLR4

Anti-SSB antibodies promotes interleukin-6 production in monocytes through a toll-like receptor4-dependent way in systemic lupus erythematosus. (PubMed, Clin Exp Rheumatol) - "Our findings demonstrate that anti-SSB antibodies promote cytokine production, particularly IL-6, in monocytes through a TLR4-dependent mechanism."

IO biomarker • Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CD14 • IL1B • IL4 • IL6 • NDUFA2 • TLR4 • TNFA

The air pollutant PM2.5 aggravates airway inflammation via NF-κB/NLRP3-induced pyroptosis: partially inhibited by the TLR4 inhibitor TAK242. (PubMed, Int Immunopharmacol) - "In the OVA-induced asthma mouse model, PM2.5 activates the NF-κB/NLRP3 pathway and induces pyroptosis, thereby exacerbating airway inflammation and hyperreactivity. It may activate the NF-κB signalling cascade through the TLR4/MyD88 pathway, upregulate critical proteins in the pyroptosis pathway, and induce pyroptosis and inflammation in respiratory epithelial Beas-2b cells, exacerbating asthma."

Journal • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL13 • IL18 • IL1B • IL4 • IL5 • MYD88 • NLRP3 • TLR4

Jing An decoction alleviates neuroinflammation in Tourette syndrome by regulating butyrate-mediated microbiota-gut-brain axis. (PubMed, Phytomedicine) - "JA alleviates TS by regulating the GBA axis through butyrate-producing bacteria. Butyrate alleviates neuroinflammation by inhibiting the TLR4/HDAC3/NF-κB pathway, thereby promoting M2 microglial polarization."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Inflammation • Movement Disorders • Psychiatry • Tourette Syndrome • HDAC3

Repurposing Antidiabetic Drugs for Gangrene: A Mendelian Randomization and Text Mining Study. (PubMed, Int J Med Sci) - "Subsequent DGI analysis revealed six genes targeted by 12 drugs (DGI score > 5), presenting them as candidates for treating DG. In conclusion, this study not only validates the causal effect of diabetes on gangrene risk but also identifies several potential therapeutic agents (CILAZAPRIL, RESATORVID, SILTUXIMAB, and OLOKIZUMAB) by integrating bioinformatics analysis, providing new directions for future clinical interventions."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

IL1A regulates MSU-induced apoptosis and inflammatory response through TLR4/MyD88/NF-κB signaling pathway. (PubMed, Int J Med Sci) - "The activation of the NLRP3 inflammasome and TLR4/MyD88/NF-κB pathways was evaluated, with TAK-242 used to assess synergistic effects... IL1A promotes cell death and inflammation in MSU-induced gout. Knockdown of IL1A mitigates these effects, suggesting it may be a potential therapeutic target for MSU-induced inflammation."

Journal • Gout • Immunology • Inflammation • Inflammatory Arthritis • Rheumatology • IL1A • MYD88 • NLRP3 • TLR4

Gut microbiota dysbiosis exacerbates heart failure by the LPS-TLR4/NF-κB signalling axis: mechanistic insights and therapeutic potential of TLR4 inhibition. (PubMed, J Transl Med) - "Gut microbiota dysbiosis exacerbates heart failure by activating myocardial inflammation through the LPS-TLR4/NF-κB signalling pathway. By modulating this pathway, TAK-242 improves cardiac function, suggesting its potential as a therapeutic target for heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • IL17A • IL1B • IL6 • RELA • TLR4 • TNFA

Wogonin Inhibits Oxidative Stress in Hypoxia-Induced hCMEC/D3 Cells Through Suppressing CXCL8-Mediated TLR4/NF-κB Pathway. (PubMed, J Biochem Mol Toxicol) - "Complementary experiments showed that co-administration with resatorvid, a pharmacological TLR4 inhibitor, potentiated wogonin's therapeutic efficacy. Our findings suggest that wogonin may serve as a potential therapeutic agent for HACE by targeting CXCL8 and modulating the TLR4/NF-κB pathway, thereby reducing inflammation and oxidative stress."

Journal • CNS Disorders • Inflammation • CXCL8 • IL1B • IL6 • TNFA

TLR4 interaction with PIEZO1 facilitates the 5-HT-mediated intestinal motility dysfunction in offspring mice induced by LPS exposure during pregnancy. (PubMed, Genes Dis) - "This process was disrupted by the TLR4 inhibitor TAK242. LPS exposure during pregnancy affected intestinal motility in offspring mice by activating TLR4 pathways in the colon and increasing 5-HT secretion from enterochromaffin cells. The effects of LPS on the intestine might be explained by the interaction between TLR4 and PIEZO1, suggesting that TLR4 is related to abnormal intestinal motility in offspring mice exposed to LPS during pregnancy."

Journal • Preclinical • TLR4

Fetuin-A increases thrombosis risk in non-alcoholic fatty liver disease by binding to TLR-4 on platelets. (PubMed, Cardiovasc Res) - "Fetuin-A emerges as a positive regulator of platelet hyperreactivity in NAFLD. Acting via TLR-4-dependent signalling pathways, plasma fetuin-A directly amplifies platelet activation and promotes in vivo thrombosis. Firsocostat, rosuvastatin, and pioglitazone abrogate these enhancing effects by reducing fetuin-A levels. The fetuin-A-inhibiting antibody presents potential therapeutic advantages to prevent thrombotic complications in NAFLD."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • Hematological Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Thrombosis • AHSG • MYD88 • TLR4

The Role of TLR4 in Lung Epithelial Cell Injury Caused by Influenza Virus Combined with Staphylococcus aureus. (PubMed, Microorganisms) - "To further explore TLR4's role, we used the inhibitor TAK-242 and a TLR4 siRNA knockdown. Both approaches reduced the inflammatory response triggered by IAV and SA stimulation. These findings suggest that TLR4 is a key mediator in the enhanced inflammation observed during IAV and SA co-infection, offering a potential target for therapeutic intervention."

Journal • Infectious Disease • Inflammation • Influenza • Respiratory Diseases • TLR4

HMGB1 as a Key Mediator in Malignant Mesothelioma and a Potential Target for Asbestos-Related Cancer Therapy. (PubMed, Toxics) - "In xenograft models, treatment with ethyl pyruvate (EP) and TAK-242 significantly suppressed tumor growth and HMGB1 expression, reinforcing their therapeutic potential. Given HMGB1's influence on both tumor cell behavior and the immune microenvironment, targeting the HMGB1-TLR4 axis may not only provide a novel therapeutic strategy for MM but also offer insights into the mechanisms underlying asbestos-induced tumorigenesis, potentially guiding future prevention and intervention strategies in asbestos-exposed populations."

IO biomarker • Journal • Mesothelioma • Oncology • Solid Tumor • HMGB1 • TLR4

TLR4 signal inhibition alleviates alkali-burn induced corneal neovascularization. (PubMed, Exp Eye Res) - "In addition, Resatorvid (Tak242), a specific inhibitor of TLR4, was used to treat AB cornea of WT mice...TLR4 inhibition alleviated AB-induced CNV, and suppressed MyD88, NF-κB, VEGF-A, and inflammation factors. These findings may provide new insights for the clinical treatment of AB-induced CNV."

IO biomarker • Journal • Inflammation • IL1B • IL6 • MYD88 • TNFA

Macrophages Atp6v0d2 regulates XBP1-mediated cholesterol metabolism to suppress metabolic dysfunction-associated steatohepatitis progression. (PubMed, Int Immunopharmacol) - "We uncovered a critical role of myeloid-specific Atp6v0d2 in maintaining hepatic lipid homeostasis and suppressing MASH progression. Targeted activation of Atp6v0d2 as a promising therapeutic strategy for MASH."

Journal • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • MERTK • XBP1

Sorafenib induces intestinal toxicity by disturbing gut microbiota and activating the LPS/TLR4/NF-κB signaling pathway in mice. (PubMed, Toxicology) - "Taken together, our study unveils a novel mechanism by which sorafenib exacerbates intestinal injury through gut microbiota dysbiosis and LPS/TLR4/NF-κB signaling pathway, while proposing TAK-242 as a promising therapeutic strategy. This study underscores the critical role of the gut microbiota in sorafenib-induced intestinal damage and offers new avenues for clinical intervention."

Journal • Preclinical • Hepatocellular Cancer • Infectious Disease • Oncology • Solid Tumor • Transplantation • TLR4

Beta-Cell Differentiation and Proliferation of Adult Islet Progenitor Cells Mediated by Exosomes Containing Microrna Released from Stressed Islets (IPITA 2025) - "Induction of cell cycle genes was enhanced by toll like receptor 4 (TLR4) inhibitor TAK242, dual-specificity tyrosine-regulated kinase (DYRK) inhibitors harmine and GNF4877, and small molecule differentiation inducer isoxazole 9 (ISX9)... Exosomes released by stressed islets turn on dedifferentiation, survival, and proliferation transcriptional profiles in IPCs by inhibition of TLR4 signaling and stimulation of the calcineurin/NFAT pathways. The results indicate potential use of exosomes for in vivo and in vitro biologics to expand islet progenitor cells for islet cell replacement therapy to prevent or reverse diabetes."

Clinical • IO biomarker • Diabetes • Metabolic Disorders • BCL2 • CCNA2 • FOXM1 • IFNG • IL1B • TNFA • TOP2A

Dietary supplementation of Lactobacillus casei alleviates permethrin exposure-induced zebrafish testis damage through modulation of TLR4/NF-κB and AKT/Nrf2 pathways: Oxidative stress, inflammation and ferroptosis. (PubMed, Pestic Biochem Physiol) - "Pharmacological validation confirmed that L. casei protection was based on dual regulation: TLR4 inhibition (via TAK-242) abolished the anti-inflammatory effects, while AKT activation (via SC79) increased Nrf2 expression...This study provides novel evidence that L. casei alleviates Per-induced testicular injury through coordinated suppression of oxidative inflammation and ferroptosis, mediated by TLR4/NF-κB inactivation and AKT/Nrf2 pathway activation. These findings advance strategies for probiotic-based interventions in aquatic toxicology."

Journal • Inflammation • GPX4 • IL1B • IL6 • NFE2L2 • SLC7A11 • TLR4 • TNFA

Gut microbiota is involved in the exacerbation of adrenal glucocorticoid steroidogenesis in diabetic animals by activation of the TLR4 pathway. (PubMed, Front Endocrinol (Lausanne)) - "Diabetes induction was achieved through the intravenous injection of alloxan, followed by treatments with antibiotic therapy or TLR4 antagonist (TAK-242) for 14 consecutive days...Furthermore, both TLR4 antagonist and TLR4 mutant mice (C3H/HeJ) induced a significant reduction in plasma corticosterone levels in diabetic mice. Our findings revealed that gut dysbiosis participates in the exacerbation of corticosterone production by diabetic animals, suggesting that therapeutic strategies that can normalize gut microbiota in diabetics represent promising therapeutic candidates for the treatment of glucocorticoid-induced comorbidities in diabetes."

IO biomarker • Journal • Diabetes • Inflammation • Metabolic Disorders • IFNB1 • IL1R1 • TLR4

Therapeutic potential of inosine in acute lung injury: mechanistic insights into TLR4 suppression and macrophage polarization. (PubMed, Phytomedicine) - "Inosine shows protective effects against ALI as it may regulate TLR4 signaling to modulate macrophage polarization, metabolic homeostasis, and inflammatory responses. This study comprehensively integrate multi-omics analysis and functional assays to reveal the direct interaction between inosine and TLR4 for the first time, and provides insights into its anti-inflammatory and immunoregulatory mechanisms."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Inflammation • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • IL18 • IL1B • IL6 • TLR4 • TNFA

Polysaccharide extract PCP1 from Polygonatum cyrtonema ameliorates cerebral ischemia-reperfusion injury in rats by inhibiting TLR4/NLRP3 pathway (PubMed, Zhongguo Zhong Yao Za Zhi) - "In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects."

IO biomarker • Journal • Preclinical • Cardiovascular • Inflammation • Ischemic stroke • Oncology • Reperfusion Injury • IL10 • IL18 • IL1B • IL6 • MYD88 • NLRP3 • TNFA • TRAF6