In vivo, the combination of RT and TAK242 significantly reduced growth of KLN205 tumors. These findings show that TLR4 inhibition enhances RT sensitivity in NSCLC.

Blockade of TLR4 signaling by the specific inhibitor TAK-242 significantly reduces the secreted IL-6/IL-8 levels and HPV replication. Overall, our results reveal a novel role of Top2α to shape the inflammatory microenvironment that benefits HPV replication, making it a promising therapeutic target for HPV-associated diseases.

Fracture models were established in Sprague-Dawley (SD) rats and intervened with the TLR-2 inhibitor C29 or the TLR-4 inhibitor TAK-242...These time-dependent effects significantly accelerated late-phase (>14d) fracture repair versus early stages (0-14d), improving bone healing parameters. Targeting TLR-2/4 accelerates fracture repair by suppressing MyD88/NF-κB-driven inflammation and optimizing the bone healing microenvironment.

TLR4 plays a critical role in cancer-associated muscle atrophy through the p38β MAPK-C/EBPβ signaling pathway in both in vitro and in vivo models. Pharmacological inhibition of TLR4 with TAK-242 effectively attenuated muscle atrophy, highlighting its potential therapeutic value.

In combination with cisplatin, TAK242 demonstrated an additive effect, increased cisplatin sensitivity in SCC154, and altered the death mechanism induced by cisplatin in SCC78 cells. In conclusion, TLR4 inhibition led to antitumor effects independent of HPV infection status or TP53 status, suggesting that TLR4 may be a broad-spectrum target for HNC therapy.

P2, N=78, Not yet recruiting, Yaqrit Ltd | Initiation date: Mar 2025 --> Sep 2025

P2, N=4, Terminated, Neurological Associates of West Los Angeles | The participant's caregiver requested for the participant to be withdrawn from the study. The investigator has decided to close out.

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.

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.

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.

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.

Additionally, TAK-242 (a TLR4 inhibitor) attenuated the promotive effects of HOXA5 silencing on ferroptosis of BEAS-2B cells and the inflammatory activation of MH-S cells. In conclusion, IGK alleviates LPS-stimulated ferroptosis in BEAS-2B cells and improves the imbalance of M1/M2 polarization in LPS-stimulated macrophages via HOXA5-mediated inhibition of the TLR4/NF-κΒ signaling pathway.