Co-administration of TAK-242 with drainage produced additional pathway suppression (combination index ≈ 0.83), approaching baseline activity levels. Collectively, these findings are consistent with, although they do not by themselves prove, an immunomodulatory contribution of subcutaneous drainage within the wound microenvironment; the implications for gynecological oncology should therefore be framed with appropriate caution pending validation in larger animal systems and in human tissue.

MHP protects against HIRI by inhibiting CIRP release, which subsequently reduces TLR4/PAD4-dependent NETosis and hepatocyte pyroptosis, thereby disrupting a self-amplifying inflammatory loop. These findings reveal a novel CIRP-NETs-pyroptosis axis as a key mechanism in HIRI and highlight potential therapeutic targets for liver I/R injury.

P1, N=20, Recruiting, University Health Network, Toronto | Not yet recruiting --> Recruiting

P2, N=203, Active, not recruiting, BioVie Inc. | Recruiting --> Active, not recruiting

These catabolic effects, including increased glycerol release, were significantly and dose-dependently attenuated by pretreatment with the specific TLR4 inhibitor TAK-242 (1 or 10 nM)...In conclusion, these findings demonstrate that extracellular PC acts as a noncanonical TLR4 agonist, driving adipocyte-specific lipolysis and apoptosis. This study provides a comprehensive molecular rationale for PC-based fat reduction and suggests that the modulation of TLR4 signaling could optimize the efficacy and safety of lipolytic therapies in clinical practice.

P2, N=60, Active, not recruiting, BioVie Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2026 --> May 2026 | Trial primary completion date: Dec 2025 --> May 2026

Chronic neuropathic pain disproportionately affects older individuals, particularly in the context of persistent oxaliplatin-induced peripheral neuropathy (OIPN); however, the molecular mechanisms sustaining this ageing-biased chronicity remain elusive...Furthermore, oral γ-glutamylcysteine or pharmacologic TLR4 blockade (TAK-242) effectively alleviated refractory hypersensitivity in aged models. These findings define the satellite glial GLRX3-HMGB1-TLR4 redox axis as a critical driver of age-biased neuropathic pain. Circulating PSSG represents a novel age-stratified clinical biomarker, and targeting this redox-sensitive pathway offers a promising therapeutic strategy for geriatric and chemotherapy-related neuropathies.

P1, N=20, Not yet recruiting, University Health Network, Toronto

Our findings underscore the critical role of TLR4 signalling in cachexia-associated muscle wasting across different disease contexts and demonstrate the efficacy of OH-CATH30, a TLR4 inhibitor, in alleviating muscle atrophy in various cachexia models.

P2, N=208, Recruiting, BioVie Inc. | Trial completion date: Jan 2026 --> Aug 2026 | Trial primary completion date: Nov 2025 --> Jun 2026

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.