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.

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