- |||||||||| eritoran (E5564) / Eisai
Preclinical, Journal: Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening. (Pubmed Central) - Aug 20, 2024
Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.
- |||||||||| eritoran (E5564) / Eisai
Journal: Effect of acute TLR4 inhibition on insulin resistance in human subjects. (Pubmed Central) - Nov 3, 2022
P2
These data do not support a role for TLR4 in insulin resistance. Future studies with a different class of TLR4 inhibitors, longer drug exposure, and/or lipid-enhancing interventions richer in saturated fats may be needed to further clarify the role of TLR4 on metabolic dysfunction in humans.
- |||||||||| eritoran (E5564) / Eisai
Is SARS-CoV-2 Associated with Worse Outcomes After Total Knee Arthroplasty? (Virtual Poster Hall) - Sep 17, 2022 - Abstract #ACRConvergence2022ACR_CONVERGENCE_2248;
However, a shorter time between TKA and clinical COVID19 was correlated with worse pain and function 6 months after TKA. Larger studies are needed to evaluate whether high-risk patients may benefit from delaying elective TKA 10-12 months after COVID19.
- |||||||||| eritoran (E5564) / Eisai
Increasing Incidence of Large Artery Manifestations in Patients with Giant Cell Arteritis, a Population-based Cohort over 70 Years (Northern Liberties Stage) - Sep 17, 2022 - Abstract #ACRConvergence2022ACR_CONVERGENCE_2106;
The incidence of aortic aneurysm/dissection has not changed over the last 7 decades. Mortality improvements may be due to earlier detection and identification of large artery manifestations.Figure 1: Cumulative incidence for time to any large artery manifestation in patients with incident GCA 1950-2016 (i.e., earliest of large artery stenosis or aortic aneurysm or aortic dissection) adjusted for the competing risk of death.
- |||||||||| eritoran (E5564) / Eisai
Increasing Incidence of Large Artery Manifestations in Patients with Giant Cell Arteritis, a Population-based Cohort over 70 Years (Virtual Poster Hall) - Sep 17, 2022 - Abstract #ACRConvergence2022ACR_CONVERGENCE_2070;
The incidence of aortic aneurysm/dissection has not changed over the last 7 decades. Mortality improvements may be due to earlier detection and identification of large artery manifestations.Figure 1: Cumulative incidence for time to any large artery manifestation in patients with incident GCA 1950-2016 (i.e., earliest of large artery stenosis or aortic aneurysm or aortic dissection) adjusted for the competing risk of death.
- |||||||||| eritoran (E5564) / Eisai
Journal: HSP60-Derived Peptide as an LPS/TLR4 Modulator: An in silico Approach. (Pubmed Central) - Apr 19, 2022
This observation is supported by binding energy obtained for the control antagonist Eritoran, close to those of Peptide-2...Based on the two computational techniques applied, interaction patterns were defined for Peptide-2. With these results, it is plausible to propose a peptidic approach for TLR4 modulation as a new innovative therapy to the treatment of TLR4-related cardiovascular diseases.
- |||||||||| eritoran (E5564) / Eisai
Clinical, Journal, IO biomarker: Targeting Toll-Like Receptors in Sepsis - From Bench to Clinical Trials. (Pubmed Central) - Mar 29, 2022
We critically analyze preclinical investigations into the role of TLRs in animal sepsis, the complexity of targeting TLRs for sepsis intervention, and the disappointing clinical trials of the TLR4 antagonist eritoran. Future Directions: Future sepsis treatments will depend on better understanding the complex biological mechanisms of sepsis pathogenesis, the high heterogeneity of septic humans as defined by clinical presentations and unique immunological biomarkers, and improved stratifications for targeted interventions.
- |||||||||| eritoran (E5564) / Eisai
Journal: Decrease in the inflammatory cytokines of LPS-stimulated PBMCs of patients with atherosclerosis by a TLR-4 antagonist in the co-culture with HUVECs. (Pubmed Central) - Mar 16, 2022
Eritoran treatment (50 μg/mL and 100 μg/mL) significantly reduced the levels of LPS-induced IL-6 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), TNF-α (P = 0.005 and P = 0.003; P = 0.007 and P = 0.005), IL-2 (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IFN-γ (P = 0.007 and P = 0.005; P = 0.005 and P = 0.004), IL-17A (P = 0.005 and P = 0.002; P = 0.005 and P = 0.002), IL-17F (P = 0.006 and P = 0.006; P = 0.005 and P = 0.005), IL-5 (P = 0.007 and P = 0.006; P = 0.007 and P = 0.007), IL-9 (P = 0.005 and P = 0.005; P = 0.005 and P = 0.005) and IL-21 (P = 0.007 and P = 0.007; P = 0.005 and P = 0.005) in stimulated HUVECs co-cultured with HC and HS PBMCs, compared to un-treated condition, respectively. Our results demonstrate that attenuating effect of Eritoran on the inflammatory responses to LPS is higher in PBMCs of patients with high stenosis, suggesting its potential role in ameliorating inflammatory conditions in atherosclerosis.
- |||||||||| eritoran (E5564) / Eisai
Journal: Contribution to development of remedies for COVID-19: focusing on Eritoran (Pubmed Central) - Jan 11, 2022
E6011 inhibits the tight binding of CD16-positive monocytes (a cell population that highly expresses the FKN receptor CX3CR1) to vascular endothelial cells, which are important for the local inflammatory response. This is expected to suppress the formation and exacerbation of vasculopathy in COVID-19.
- |||||||||| resatorvid (TAK-242) / Takeda, Akaza Bioscience, eritoran (E5564) / Eisai
Preclinical, Journal: Switch Off "Parallel Circuit": Insight of New Strategy of Simultaneously Suppressing Canonical and Noncanonical Inflammation Activation in Endotoxemic Mice. (Pubmed Central) - Aug 13, 2021
However, potent TLR4 inhibitors TAK-242 and Eritoran have been terminated in phase III clinical trials because of inadequate efficacy...To verify the strategy, two potential compounds are found: Luteolin and Diacerein with substantial antiinflammatory activity in vitro and in vivo...Notably, Luteolin exhibits better antiinflammatory activity than TAK-242 at comparable TLR4-inhibitory levels. These findings indicate that simultaneous inhibition of TLR4 and caspase-4/5/11 can be an anticipative strategy defeating sepsis and endotoxemia, which can be translated into significant medical and economic benefits.
- |||||||||| eritoran (E5564) / Eisai
[VIRTUAL] Evaluating the Prospective Predictive Value of Biopsychosocial Indices of Sensitivity to Physical Activity among People with Back Pain () - Jun 29, 2021 - Abstract #IASP2021IASP_675;
Hull & East Yorkshire Hospital, Anlaby Road, Hull HU3 2JZ, United Kingdom.Barriers to treatment adherence in physiotherapy outpatient clinics: a systematic reviewManual TherapyManual TherManual TherapyManual TherManual TherapyManual Ther220-8153Ambulatory CareHumans*Musculoskeletal Diseases/rh [Rehabilitation]*Patient Compliance*Physical Therapy Modalities2010Jun1532-276920163979Reviewhttp://ac.els-cdn.com/S1356689X09002094/1-s2.0-S1356689X09002094-main.pdf?_tid=5ad87f30-893d-11e6-a95b-00000aab0f6b&acdnat=1475480909_83780d1b28137c737ccec70de809c833English3 SPA refers to negative biopsychosocial responses to physical activity, such as daily life activities and rehabilitation exercises. 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4-6 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061696 3C2F746974 Source of Financial
- |||||||||| eritoran (E5564) / Eisai
[VIRTUAL] Evaluating the Porcine Evoked Pain Scale in a Preclinical Model () - Jun 29, 2021 - Abstract #IASP2021IASP_627;
This scoring system confirms measurable differences in painful responses in healthy and normally behaving animals. This analysis demonstrates that presumed pressure-sensitive areas of the gastrocnemius and cheek are less pressure tolerant than areas such as the trapezius, but also suggests that the skin overlying these areas may be equally sensitive to pinprick.
- |||||||||| Soliris (eculizumab) / Alexion Pharma
Journal: Combined blockade of complement C5 and TLR co-receptor CD14 synergistically inhibits pig-to-human corneal xenograft induced innate inflammatory responses. (Pubmed Central) - Jun 1, 2021
C5-blockade by eculizumab inhibited all the cytokines except G-CSF when induced by NPC...Finally, by using the TLR4 specific inhibitor Eritoran, we showed that TLR4 activation was the basis for the CD14 effect...Intriguingly, the inflammatory response was efficiently blocked by simultaneously targeting bottleneck molecules in the complement system (C5) and the TLR co-receptor CD14 with pharmaceutical inhibitors. We postulate that a combination of C5 and CD14 inhibition could have a great therapeutic potential to overcome the immunologic barrier in pig-to-human corneal xenotransplantation.
- |||||||||| eritoran (E5564) / Eisai
Clinical, Journal, IO biomarker: Dissociation of TRIF bias and adjuvanticity. (Pubmed Central) - Apr 28, 2021
Despite these differences, sMPL and E6020 adjuvants enhanced antibody responses to comparable extents, with balanced immunoglobulin (Ig) isotypes in two immunization models. These data indicate that a TRIF bias is not necessarily predictive of superior adjuvanticity.
- |||||||||| eritoran (E5564) / Eisai
Review, Journal: Increasing the Chemical Variety of Small-Molecule-Based TLR4 Modulators: An Overview. (Pubmed Central) - Apr 13, 2021
Some "old" TLR4 agonists or antagonists such as MPLA or Eritoran are under study for repositioning in different pharmacological contexts. The mechanism of action of the molecules and the level of TLR4 involvement in their biological activity are critically discussed.
- |||||||||| eritoran (E5564) / Eisai
Biomarker, Journal: Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis. (Pubmed Central) - Sep 16, 2020
The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database...miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.
- |||||||||| eritoran (E5564) / Eisai
[VIRTUAL] Sporadic Phaeochromocytoma, Pancreatic Neuroendocrine Tumour and a Sacral Hibernoma: A Case Report () - Jun 20, 2020 - Abstract #ENDOI2020ENDO-I_2427;
The adrenal lesion was biochemically suggestive of a phaeochromocytoma (plasma normetanephrine 4930 pmol/L, plasma 3-methoxytyramine 580 pmol/L, urinary noradrenaline 5564 pmol/day, urinary dopamine 4720 nmol/day)...Genetic testing revealed no identifiable genetic mutations.This case reports the synchronous presence of a phaeochromocytoma, pancreatic NET and sacral hibernoma with no identifiable genetic mutation. To date, the association between hibernomas and neuroendocrine tumours has not been fully established, but a few case reports suggest a possible association between MEN1 and hibernomas.
- |||||||||| eritoran (E5564) / Eisai
Sporadic Phaeochromocytoma, Pancreatic Neuroendocrine Tumour and a Sacral Hibernoma: A Case Report (ENDOExpo, Booth 217) - Apr 1, 2020 - Abstract #ENDO2020ENDO_4279;
The adrenal lesion was biochemically suggestive of a phaeochromocytoma (plasma normetanephrine 4930 pmol/L, plasma 3-methoxytyramine 580 pmol/L, urinary noradrenaline 5564 pmol/day, urinary dopamine 4720 nmol/day)...Genetic testing revealed no identifiable genetic mutations.This case reports the synchronous presence of a phaeochromocytoma, pancreatic NET and sacral hibernoma with no identifiable genetic mutation. To date, the association between hibernomas and neuroendocrine tumours has not been fully established, but a few case reports suggest a possible association between MEN1 and hibernomas.
- |||||||||| eritoran (E5564) / Eisai
Sporadic Phaeochromocytoma, Pancreatic Neuroendocrine Tumour and a Sacral Hibernoma: A Case Report (ENDOExpo) - Feb 7, 2020 - Abstract #ENDO2020ENDO_3099;
The adrenal lesion was biochemically suggestive of a phaeochromocytoma (plasma normetanephrine 4930 pmol/L, plasma 3-methoxytyramine 580 pmol/L, urinary noradrenaline 5564 pmol/day, urinary dopamine 4720 nmol/day)...Genetic testing revealed no identifiable genetic mutations.This case reports the synchronous presence of a phaeochromocytoma, pancreatic NET and sacral hibernoma with no identifiable genetic mutation. To date, the association between hibernomas and neuroendocrine tumours has not been fully established, but a few case reports suggest a possible association between MEN1 and hibernomas.
- |||||||||| NN1213 / Novo Nordisk, eritoran (E5564) / Eisai
Trial completion, Enrollment change: Eritoran1: The Role of TLR4 on Lipid-induced Insulin Resistance (clinicaltrials.gov) - Oct 8, 2019
P2, N=10, Completed,
Despite control of seizure with MgSO, the incidence of neurological complications remains high. Terminated --> Completed | N=16 --> 10
- |||||||||| Kineret (anakinra) / SOBI, Affibody, eritoran (E5564) / Eisai
Journal: Altered colonic sensory and barrier functions by CRF: roles of TLR4 and IL-1. (Pubmed Central) - Sep 12, 2019
CRF induced these visceral changes via TLR4 and cytokine system, which were CRF dependent, and activation of CRF inhibited these CRF-triggered responses. CRF may modulate immune system to alter visceral changes, which are considered to be pivotal pathophysiology of IBS.
- |||||||||| eritoran (E5564) / Eisai
Journal: Influenza "Trains" the Host for Enhanced Susceptibility to Secondary Bacterial Infection. (Pubmed Central) - Aug 9, 2019
Both type I IFN and neutrophil dysfunction through decreased chemokine production have been implicated as mechanisms underlying enhanced susceptibility to 2° bacterial infections. Our findings support the conclusion that selective suppression of CXCL1/CXCL2 represents an IFN-β-mediated "training" of the macrophage transcriptional response to TLR2 agonists and that blocking of TLR4 therapeutically with Eritoran after influenza virus infection reverses this suppression by blunting influenza-induced IFN-β.
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