BJIKT synergistically promotes M1-like macrophage activation through partial TLR4 dependence and elicits antitumor effects via macrophage-derived cytokines. These findings provide insight into how a traditional multi-herbal formula can influence macrophage activation and cytokine-mediated antitumor responses.

The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L-1), a specific TLR4 blocker, against S1 (10 µmol·L-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL-1) to elucidate the TLR4 pathway's mediating role...S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

P2, N=0, Withdrawn, Allodynic Therapeutics, Inc | N=300 --> 0 | Trial completion date: Dec 2026 --> Dec 2025 | Recruiting --> Withdrawn | Trial primary completion date: Dec 2026 --> Dec 2025

In this study, we demonstrated that temozolomide (TMZ) could activate the autophagy-dependent secretory pathway to promote extracellular secretion of Alpha-enolase (ENO1)...Importantly, in vivo studies confirmed that combined therapy with the SPHK1 inhibitor PF-543, the TLR4 antagonist TAK-242, and TMZ synergistically suppressed tumor growth and significantly enhanced the efficacy of TMZ. Collectively, these findings reveal that ENO1 mediates intercellular crosstalk between GBM cells and M2-TAMs via autophagy-dependent secretion, thereby driving TMZ chemoresistance and functioning as an oncogene in GBM. Targeting the ENO1/TLR4 signaling axis reshapes the immune microenvironment and enhances the efficacy of TMZ, offering a promising therapeutic strategy and potential combinatorial targets for precision therapy in GBM.

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.