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DRUG CLASS:

TLR4 antagonist

24d
Curcumin as a palliative treatment for malignant pleural effusion (ACTRN12620001216909)
P1, N=9, Withdrawn, Flinders University | Recruiting --> Withdrawn
Trial withdrawal
28d
New P2 trial
|
Avastin (bevacizumab)
1m
New P2 trial
1m
Recent progress on small molecule TLR4 antagonist against triple-negative breast cancer progression and complications. (PubMed, Bioorg Med Chem)
This review summarizes recent advancements in the development of small-molecule TLR4 antagonists to suppress TNBC growth, metastasis, and chemotherapy resistance. We also examine their potential in managing cancer-related complications and propose future directions for their application in TNBC therapy.
Review • Journal
|
TLR4 (Toll Like Receptor 4)
2ms
ATP citrate lyase ablation hampers exocrine regeneration via TLR4/NF-kappaB signaling after acute pancreatitis in mice. (PubMed, Int Immunopharmacol)
The present study demonstrated that ablation of pancreatic Acly intensified inflammatory reaction and cell death, and dampened exocrine regeneration following AP, due to the positive regulation of TLR4/NF-κB signaling activation.
Preclinical • Journal • IO biomarker
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CASP3 (Caspase 3) • TLR4 (Toll Like Receptor 4) • ACLY (ATP Citrate Lyase) • IL1B (Interleukin 1, beta) • RELA (RELA Proto-Oncogene)
|
RELA expression
3ms
Muti-target rationale design of novel substituted N-phenyl-2-((6-phenylpyridazin-3-yl)thio)acetamide candidates as telomerase/JAK1/STAT3/TLR4 inhibitors: In vitro and in vivo investigations. (PubMed, Bioorg Chem)
In this work, additional effort was applied to design new BIBR1532-based analogues with potential inhibitory activity against telomerase and acting as multitarget antitumor candidates to overcome the resistance problem...Compound 4l represented a very promising JAK1 inhibitory potential with a 0.46-fold change, compared to that of pacritinib reference standard (0.33-fold change). Besides, it showed a superior STAT3-inhibitory potential with a 0.22-fold change compared to sorafenib (0.33-fold change). Additionally, compound 4l downregulated TLR4 protein expression by 0.81-fold change compared to that of resatorvid (0.29-fold change)...Remarkably, compound 4l led to prominent reductions in tumor size and mass. Concurrent enhancements in biochemical, hematologic, histopathologic, and immunohistochemical parameters further confirmed the suppression of angiogenesis and inflammation, elucidating additional mechanisms by which compound 4l exerts its anticancer effects.
Preclinical • Journal
|
JAK1 (Janus Kinase 1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • TLR4 (Toll Like Receptor 4)
|
sorafenib • Vonjo (pacritinib) • BIBR1532
4ms
Mechanism of Extracellular Histone-Induced Endothelial Dysfunction Leading to Sepsis-Induced Acute Respiratory Distress Syndrome (PubMed, Sichuan Da Xue Xue Bao Yi Xue Ban)
Then, HUVEC were exposed to histones at an optimal concentration with or without resatorvid (TAK-242), a selective inhibitor of Toll-like receptor 4 (TLR4), for 24 hours for modeling...By binding to TLR-4, histone decreases VE-cadherin expression on the surface of vascular endothelial cells, disrupts the integrity of intercellular adherens junctions, and triggers pathological damage to lung tissue. Using TLR-4 inhibitors can prevent sepsis-induced ARDS in histone-induced sepsis.
Journal • IO biomarker
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • TLR4 (Toll Like Receptor 4) • CDH5 (Cadherin 5)
5ms
A phase 2, open-label study of anti-inflammatory NE3107 in patients with dementias. (PubMed, Medicine (Baltimore))
Our results indicate that in this study NE3107 was associated with what appear to be positive neurophysiological and neuropsychological findings, as well as evidence of improvement in biomarkers associated with neuroinflammation and AD in patients diagnosed with dementia. Our findings are consistent with previous preclinical and clinical observations and highlight a central role of neuroinflammation in AD pathogenesis.
P2 data • Journal
|
TNFA (Tumor Necrosis Factor-Alpha)
|
Triolex (bezisterim)
5ms
Shenfu Injection regulates macrophage polarization via TLR4/NF-κB pathway to reduce inflammation in chronic heart failure (PubMed, Zhongguo Zhong Yao Za Zhi)
The modeled mice were randomly divided into the model group, Shenfu Injection group, and TAK-242 group, and were injected intraperitoneally with the corresponding drugs for 15 days...CHF mice have an imbalance of M1/M2 macrophage polarization, with M1-type macrophages predominating. Shenfu Injection promotes macrophage polarization towards M2, inhibits M1-type macrophage activation, and attenuates inflammatory responses in heart failure by regulating the TLR4/NF-κB signaling pathway.
Journal • IO biomarker
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CD163 (CD163 Molecule) • IL10 (Interleukin 10) • ITGAM (Integrin, alpha M) • TLR4 (Toll Like Receptor 4) • CD86 (CD86 Molecule)
5ms
Insulin-sensitizing NE3107 in Improving Sleep and Fatigue in Subjects With Traumatic Brain Injury (clinicaltrials.gov)
P2, N=5, Recruiting, Neurological Associates of West Los Angeles | Not yet recruiting --> Recruiting | Phase classification: P2a --> P2 | Trial completion date: Jul 2024 --> Jul 2025 | Initiation date: Aug 2023 --> Dec 2023 | Trial primary completion date: Jun 2024 --> Dec 2024
Enrollment open • Phase classification • Trial completion date • Trial initiation date • Trial primary completion date
|
Triolex (bezisterim)
6ms
New P2 trial
|
IL6 (Interleukin 6) • IL17A (Interleukin 17A)
|
mosedipimod (EC-18)
6ms
IL-6 knockdown in a model of the human bone marrow, abrogates DNA damage induction in bystander cells post-chemotherapy induced cytokine release syndrome. (PubMed, Transl Oncol)
During HSCT, haematopoietic cells are exposed to a complex mix of cytokines, so to determine if IL-6 was integral in a chemotherapy-induced bystander effect, we attempted to inhibit IL-6 from HS-5 cells using resatorvid or siRNA, treated with chlorambucil or mitoxantrone, and then co-cultured with bystander TK6 cells. Our data suggests that exposure to high IL-6 (in the absence of inflammatory cells) has potential to induce genetic damage and may contribute to de novo tumorigenesis post-CS. We suggest that for individuals with a pro-inflammatory profile, anti-IL-6 therapy may be an appropriate intervention to prevent complications post-CS.
Journal
|
IL6 (Interleukin 6)
|
mitoxantrone • Leukeran (chlorambucil)
7ms
ApTOLL: A new therapeutic aptamer for cytoprotection and (re)myelination after multiple sclerosis. (PubMed, Br J Pharmacol)
Our findings reveal a new therapeutic approach for the treatment of inflammatory and demyelinating diseases such as MS. The molecular nature of the aptamer exerts not only an anti-inflammatory effect but also neuroprotective and remyelinating effects. The excellent safety profile demonstrated by ApTOLL in animals and humans opens the door to future clinical trials in MS patients.
Journal
|
TLR4 (Toll Like Receptor 4)
8ms
Hangeshashinto Inhibits Porphyromonas gingivalis Pathogen-Associated Molecular Patterns-Mediated IL-6 and IL-8 Production through Toll-Like Receptors in CAL27 Cells. (PubMed, Evid Based Complement Alternat Med)
Hangeshashinto, like Toll-like receptor (TLR) signaling inhibitors (resatorvid and C29) and an immunosuppressant (dexamethasone), exhibited the ability to suppress TLR-mediated activation of the transcription factor nuclear factor-κB (NF-κB) in response to PAMP stimulation. This study suggests that the anti-inflammatory effects of hangeshashinto may be attributed to the inhibition of TLR signal transduction pathways including NF-κB activation, thereby suppressing NF-κB-dependent gene expression.
Journal • IO biomarker
|
IL6 (Interleukin 6) • CXCL8 (Chemokine (C-X-C motif) ligand 8)
|
dexamethasone
8ms
Jiedu Xiaozheng Yin Inhibits the Progression of Colitis Associated Colorectal Cancer by Stimulating Macrophage Polarization Towards an M1 Phenotype via the TLR4 Pathway. (PubMed, Integr Cancer Ther)
Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1β mRNA were detected by RT-qPCR. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1β after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.
Journal
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL10 (Interleukin 10) • IL1B (Interleukin 1, beta) • MRC1 (Mannose Receptor C-Type 1) • CD80 (CD80 Molecule) • CD86 (CD86 Molecule)
|
IL6 expression
|
LY294002
9ms
Modulating the Mesenchymal Stromal Cell Microenvironment Alters Exosome RNA Content and Ligament Healing Capacity. (PubMed, Stem Cells)
In this study, we used an in vitro system to compare the priming of human MSCs by two inflammatory inducers TNF-α and CRX-527 (a highly potent synthetic TLR4 agonist that can be used as a vaccine adjuvant or to induce anti-tumor immunity) on exosome molecular cargo, as well as on an in vivo rat ligament injury model to validate exosome potency...Additionally, a link was identified between altered exosomal microRNA levels and expression changes in microRNA targets in ligaments. These findings elucidate the nuanced interplay between MSCs, their exosomes, and tissue regeneration.
Journal • Stroma
|
TNFA (Tumor Necrosis Factor-Alpha) • TLR4 (Toll Like Receptor 4)
|
TLR4 modulator program
9ms
Indole-3-Carbinol Promotes Apoptosis and Inhibits the Metastasis of Esophageal Squamous Cell Carcinoma by Downregulating the Wnt/β-Catenin Signaling Pathway. (PubMed, Nutr Cancer)
MTT and flow cytometry were used to assess cell viability and apoptosis in EC18 and TE1 cells, while wound healing and transwell assays were used to investigate cell migration and invasion in vitro...I3C promoted ESCC apoptosis and inhibited cell migration and invasion by downregulating β-catenin, c-myc, and cyclin D1 in vitro and decreased the tumor growth in vivo; this process was reversed by LiCl treatment. In summary, I3C inhibits ESCC malignant behavior by suppressing the Wnt/β-catenin signaling pathway, thus deeming it a promising drug for ESCC treatment.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CCND1 (Cyclin D1)
|
MYC expression • CCND1 expression
|
mosedipimod (EC-18)
9ms
Impacts of monosaccharide composition on immunomodulation by cello-pentaose, manno-pentaose, and xylo-pentaose: Unraveling the underlying molecular mechanisms. (PubMed, Carbohydr Polym)
The TLR4-dependent immunoregulatory effect of functional oligosaccharides was shown by measuring the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in RAW264.7 cells treated with different functional oligosaccharides, both with and without Resatorvid [TAK-242] (a Toll-like receptor 4 [TLR4] inhibitor)...The fluorescence spectra and molecular docking results revealed that the main mechanisms by which these oligosaccharides attach to the TLR4 active pocket are hydrogen bonds and van der Waals forces. Functional oligosaccharides were ranked according to their affinity for TLR4, as follows: MOS > COS > XOS, indicating that oligosaccharides or polysaccharides containing mannose units may confer significant advantages for immune enhancement.
Journal • Immunomodulating
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • TLR4 (Toll Like Receptor 4)
9ms
Multi-Center Study of Naltrexone-Acetaminophen in Acute Migraine, With an Exploratory Analysis of Co-occurring Anxiety (clinicaltrials.gov)
P2, N=300, Not yet recruiting, Allodynic Therapeutics, Inc | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Mar 2025 --> Jul 2026
Trial completion date • Trial primary completion date
10ms
ALMA: Anti Inflammatory Lipid Mediators in Asthma Lipid Anti-Inflammtory Mediators in Asthma (clinicaltrials.gov)
P2, N=60, Recruiting, University of Colorado, Denver | Trial completion date: Jan 2029 --> Jan 2030 | Trial primary completion date: Nov 2028 --> Nov 2029
Trial completion date • Trial primary completion date
10ms
ANODYNE-1: An Acute Migraine Factorial Study (clinicaltrials.gov)
P2, N=92, Completed, Allodynic Therapeutics, Inc
New P2 trial
11ms
High mobility group nucleosome binding protein 1 (HMGN1) induces activation of mouse BV2 microglia and upregulates their pro-inflammatory mediator expression by activating TLR4/MyD88/NF-κB p65/IKK-β signal pathway (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi)
The cells in the model group were treated with 500 ng/mL HMGN1, while the antagonist group was treated with 500 ng/mL TAK-242 (resatorvid), a Toll-like receptor 4 (TLR4) antagonist, in addition to HMGN1...The results of Western blot suggested that the protein expression levels of iNOS, TLR4, MyD88, NF-κB p65 and IKK-β decreased significantly in the antagonist group. Conclusion HMGN1 may induce the activation of BV2 microglial cells by upregulating pro-inflammatory mediators through activating the TLR4/MyD88/NF-κB p65/IKK-β signaling pathway.
Preclinical • Journal • IO biomarker
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CCL2 (Chemokine (C-C motif) ligand 2) • TLR4 (Toll Like Receptor 4) • IL1B (Interleukin 1, beta) • MRC1 (Mannose Receptor C-Type 1) • HMGN1 (High Mobility Group Nucleosome Binding Domain 1)
11ms
Pro-neuroinflammatory and neurotoxic potential of extracellular histones H1 and H3. (PubMed, Neurosci Res)
The selective inhibitors MMG-11 and TAK-242 were used to demonstrate involvement of toll-like receptors (TLR) 2 and 4, respectively, in H1-induced NO secretion by BV-2 microglia...We conclude that H1, and to a lesser extent H3, when released extracellularly, have the potential to act as a CNS DAMPs. Inhibition of the DAMP-like effects of extracellular histones on microglia and their neurotoxic activity represents a potential strategy for combating neurodegenerative diseases that are characterized by the adverse activation of microglia and neuronal death.
Journal
|
IFNG (Interferon, gamma) • TNFA (Tumor Necrosis Factor-Alpha)
1year
Multi-Center Study of Naltrexone-Acetaminophen in Acute Migraine, With an Exploratory Analysis of Co-occurring Anxiety (clinicaltrials.gov)
P2, N=300, Not yet recruiting, Allodynic Therapeutics, Inc | Trial completion date: Nov 2024 --> Jul 2025 | Trial primary completion date: Sep 2024 --> Mar 2025
Trial completion date • Trial primary completion date
1year
Subcutaneous Streptococcus dysgalactiae GAPDH vaccine in mice induces a proficient innate immune response. (PubMed, J Vet Sci)
GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.
Preclinical • Journal
|
IL10 (Interleukin 10) • TLR4 (Toll Like Receptor 4) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase) • TLR2 (Toll Like Receptor 2)
1year
Ginsenoside-Re inhibits experimental autoimmune encephalomyelitis as a mouse model of multiple sclerosis by downregulating TLR4/MyD88/NF-κB signaling pathways. (PubMed, Phytomedicine)
G-Re might alleviate motor impairment of EAE and its pathological/inflammatory events in the spinal cord by preventing BBB disruption via downregulation of TLR4/MyD88/NF-κB signaling pathways. These findings for the first time suggest that G-Re might be a potential therapeutic for MS through maintenance of BBB integrity.
Preclinical • Journal • IO biomarker
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • IL6 (Interleukin 6) • TLR4 (Toll Like Receptor 4) • CD31 (Platelet and endothelial cell adhesion molecule 1) • IL1B (Interleukin 1, beta) • TJP1 (Tight Junction Protein 1) • OCLN (Occludin)
1year
A Phase 3 Study of NE3107 in Probable Alzheimer's Disease (clinicaltrials.gov)
P3, N=439, Completed, BioVie Inc. | Active, not recruiting --> Completed | N=316 --> 439
Trial completion • Enrollment change
|
TNFA (Tumor Necrosis Factor-Alpha) • APOE (Apolipoprotein E) • CRP (C-reactive protein) • GFAP (Glial Fibrillary Acidic Protein) • LEP (Leptin)
|
Triolex (bezisterim)
1year
Lactobacillus casei combined with Lactobacillus reuteri alleviate pancreatic cancer by inhibiting TLR4 to promote macrophage M1 polarization and regulate gut microbial homeostasis. (PubMed, BMC Cancer)
L. casei & L. reuteri alleviate pancreatic cancer by inhibiting TLR4 to promote macrophage M1 polarization and regulate gut microbial homeostasis.
Journal
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • TLR4 (Toll Like Receptor 4)
1year
Blinded response data from the phase 3 NM101 trial of anti-inflammatory bezisterim (NE3107) in patients with mild to moderate Alzheimer’s disease (Neuroscience 2023)
These data suggest that the pathophysiology of dementia and cognitive impairment in probable AD are driven by inflammatory factors that are present in both Aβ-positive and -negative populations. Additionally, the study findings suggest that the current diagnostic criteria for AD based on Aβ status may be too stringent and may inadvertently prevent development of therapies for patients with probable AD.
Clinical • P3 data
|
CRP (C-reactive protein)
|
Triolex (bezisterim)
1year
TLR4 Inhibition Protects against Retinal Ganglion Cell Damage in Rats with Chronic Ocular Hypertension. (PubMed, Discov Med)
Targeting TLR4 inhibition could be a potential therapeutic strategy to protect RGCs from COH damage.
Preclinical • Journal • IO biomarker
|
IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • TLR4 (Toll Like Receptor 4) • IL1B (Interleukin 1, beta) • NLRP3 (NLR Family Pyrin Domain Containing 3)
over1year
Herbal melanin modulates PGE2 and IL-6 gastroprotective markers through COX-2 and TLR4 signaling in the gastric cancer cell line AGS. (PubMed, BMC Complement Med Ther)
A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.
Preclinical • Journal • IO biomarker
|
IL6 (Interleukin 6) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • MUC4 (Mucin 4, Cell Surface Associated)
|
MUC4 expression • PTGS2 expression • IL6 expression
over1year
HMGB1-mediated elevation of KLF7 facilitates hepatocellular carcinoma progression and metastasis through upregulating TLR4 and PTK2. (PubMed, Theranostics)
The combined application of TLR4 inhibitor TAK-242 and PTK2 inhibitor defactinib alleviates HCC progression and metastasis induced by the HMGB1-KLF7 axis. HMGB1-induced KLF7 overexpression facilitates HCC progression and metastasis by upregulating TLR4 and PTK2. Genetic ablation of KLF7 via AAV gene therapy and combined blockade of TLR4 and PTK2 represents promising therapy strategies for KLF7-positive HCC patients.
Journal • IO biomarker
|
HMGB1 (High Mobility Group Box 1) • TLR4 (Toll Like Receptor 4) • TYK2 (Tyrosine Kinase 2) • AGER (Advanced Glycosylation End-Product Specific Receptor) • PTK2 (Protein Tyrosine Kinase 2)
|
HMGB1 overexpression
|
defactinib (VS-6063)
over1year
Quality of life (QoL) and toxicity in patients (pts) with hormone receptor-positive, HER2-negative early breast cancer (HR+, HER2– eBC) treated with adjuvant (adj) endocrine therapy (ET) in the CANcer TOxicities (CANTO) study (ESMO 2023)
Results Of the 5564 pts who met the inclusion criteria (median age: 57 yrs), 63% were post-menopausal and 52% had stage I eBC at diagnosis...This study confirmed long-term toxicity of ET, particularly pain. Better management of symptoms and supportive interventional strategies are needed to further improve QoL in eBC.
Clinical • HEOR
|
HER-2 (Human epidermal growth factor receptor 2)
|
HR positive • HER-2 negative • HR positive + HER-2 negative
|
eritoran (E5564)
over1year
Lipopolysaccharide exacerbates to the migration, invasion, and epithelial-mesenchymal transition of esophageal cancer cells by TLR4/NF-κB axis. (PubMed, Environ Toxicol)
However, TAK242 (TLR4 inhibitor) or PDTC (NF-κB inhibitor) could eliminate the inflammatory and EMT-promoting effects of LPS. In total, our results suggested that LPS exacerbated to the migration, invasion, and epithelial-mesenchymal transition of EC109 cells by TLR4/NF-κB axis. High level LPS may have a critical effect on the occurrence and development of EC.
Journal
|
IL6 (Interleukin 6) • CDH1 (Cadherin 1) • VIM (Vimentin) • TGFB1 (Transforming Growth Factor Beta 1) • TLR4 (Toll Like Receptor 4) • CDH2 (Cadherin 2)
almost2years
HMGB1-MEDIATED ELEVATION OF KLF7 FACILITATES HEPATOCELLULAR CARCINOMA PROGRESSION AND METASTASIS THROUGH TLR4 AND PTK2 (DDW 2023)
Combined application of TLR4 inhibitor TAK-242 and PTK2 inhibitor defactinib alleviated HCC progression and metastasis mediated by the HMGB1-KLF7 axis. HMGB1-induced KLF7 overexpression facilitated HCC progression and metastasis by upregulating TLR4 and PTK2 expression. Combined administration of TLR4 and PTK2 inhibitors, or genetic ablation of KLF7 via AAV gene therapy represented promising therapy strategies for KLF7-positive HCC patients.
IO biomarker
|
HMGB1 (High Mobility Group Box 1) • TLR4 (Toll Like Receptor 4) • TYK2 (Tyrosine Kinase 2) • AGER (Advanced Glycosylation End-Product Specific Receptor) • PTK2 (Protein Tyrosine Kinase 2)
|
defactinib (VS-6063)
almost2years
Multi-Modal Correlation Analyses From a Phase 2, Open-Label Study of NE3107 in Patients With Cognitive Decline Due to Degenerative Dementias (AAN 2023)
Conclusions Correlations among improved cognitive function, reduced inflammation, and changes in the clinician-observed GRC (overall impression of patient’s abilities) were consistent with the hypothesized activities of NE3107. Preliminary examination of metabolic and functional brain imaging supports hypothesis-based directional changes in accordance with the expected mechanism of action.
Clinical • P2 data
|
TNFA (Tumor Necrosis Factor-Alpha)
|
Triolex (bezisterim)
2years
Mechanisms and treatments of neuropathic itch in a mouse model of lymphoma. (PubMed, J Clin Invest)
Intrathecal gabapentin injection reduced late-phase but not early-phase pruritus...Collectively, we have established a mouse model of neuropathic and cancer itch with relevance to human disease. Our findings also suggest distinct mechanisms underlying acute, chronic, and neuropathic itch.
Preclinical • Journal
|
CD123 (Interleukin 3 Receptor Subunit Alpha) • TLR4 (Toll Like Receptor 4) • TRPV1 (Transient Receptor Potential Cation Channel Subfamily V Member 1) • IL1R1 (Interleukin 1 receptor, type I)
2years
Exosomes from Crx-527 Stimulated MSCs Suppress T Cell Activation and Xenogeneic Gvhd While Preserving GVL (TCT-ASTCT-CIBMTR 2023)
CRX-exosomes are superior to exosomes from unstimulated MSCs at preventing xenogeneic GVHD. Interestingly, CRX-exosome treatment does not prevent GVL activity despite the induction of Tregs. CRX-exosome treatment does not directly alter T cell biology but does cause dramatic differences in the transcriptome of monocytes, increasing IL-6 and IL-10 expression which may impact T cell activation.
IO biomarker
|
IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2RA (Interleukin 2 receptor, alpha) • CD4 (CD4 Molecule) • IL10 (Interleukin 10) • TLR4 (Toll Like Receptor 4)
|
IL6 expression
|
TLR4 modulator program
2years
Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice. (PubMed, Immunopharmacol Immunotoxicol)
In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.
Preclinical • Journal • IO biomarker
|
TLR4 (Toll Like Receptor 4)
2years
The gut microbiota - a vehicle for the prevention and treatment of hepatocellular carcinoma. (PubMed, Biochem Pharmacol)
The clinical development of TLR4 antagonists is urgently needed to counteract the pathological effects of dysbiosis on the liver and other organs. Further nutrigenomic studies are required to understand better how the diet influences the gut microbiota and its adverse effects on the liver.
Review • Journal
|
TLR4 (Toll Like Receptor 4)
2years
Involvement of TLR2-TLR4, NLRP3, and IL-17 in pain induced by a novel Sprague-Dawley rat model of experimental autoimmune encephalomyelitis. (PubMed, Front Pain Res (Lausanne))
Then, 2 weeks later, rats began daily subcutaneous injections of the Toll-like receptor 2 and 4 (TLR2-TLR4) antagonist (+)-naltrexone [(+)-NTX] or saline for an additional 13 days...These findings characterize an optimized MOG-induced SD rat model of EAE for the study of pain with minimal motor impairments/disabilities. Finally, these studies support the role of TLR2-TLR4 antagonists as a potential treatment for MS-related pain and other pain and inflammatory-related disorders.
Preclinical • Journal
|
TLR4 (Toll Like Receptor 4) • IL17A (Interleukin 17A) • NLRP3 (NLR Family Pyrin Domain Containing 3) • TLR2 (Toll Like Receptor 2)
|
naltrexone