Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies
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INTRODUCTION: Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs that inhibit the pro-inflammatory effects of lipopolysaccharide (LPS) and improve outcome when added to conventional sepsis treatments are lacking. Eritoran tetrasodium (E5564) is a promising candidate therapy for sepsis belonging to a new class of such drugs which inhibit LPS-induced inflammation by blocking toll-like receptor 4. AREAS COVERED: This review focuses on the rationale for the use of eritoran tetrasodium in sepsis as well as on its pharmacokinetics, pharmacodynamics, efficacy and safety. Preclinical and clinical studies from a MEDLINE/PubMed literature search in August 2010 with the search terms 'eritoran' and 'E5564' are discussed. EXPERT OPINION: Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. While early clinical results are promising, its efficacy and safety for treating patients with sepsis are currently under investigation. Even if the ongoing Phase III clinical trial enrolling patients with severe sepsis and increased risk of death shows benefit from eritoran, questions remain and confirmatory studies would be necessary to define its clinical usage.
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Eritoran and resatorvid improved survival in animal sepsis models but did not reduce mortality in patients with severe sepsis.
“Eritoran130 and resatorvid131 improved survival in animal models of sepsis, but did not reduce mortality in patients with severe sepsis132,133.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [130]
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Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394 · see citing works
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · see citing works
Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis
Bernard, G. R., Vincent, J., Laterre, P., LaRosa, S. P., Dhainaut, J.-F., Lopez-Rodriguez, A., Steingrub, J. S., Garber, G. E., Helterbrand, J. D., Ely, E. W., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103083441001 · Cited by 6,124 · see citing works
Toll-like receptors: critical proteins linking innate and acquired immunity
Akira, S., Takeda, K., & Kaisho, T. (2001) · Nature Immunology · doi:10.1038/90609 · Cited by 4,777 · see citing works
Toll-like receptors in the induction of the innate immune response
Aderem, A. A., & Ulevitch, R. J. (2000) · Nature · doi:10.1038/35021228 · Cited by 3,047 · see citing works
The structural basis of lipopolysaccharide recognition by the TLR4–MD-2 complex
Park, B., Song, D., Kim, H. M., Choi, B.-S., Lee, H., & Lee, J.-O. (2009) · Nature · doi:10.1038/nature07830 · Cited by 2,421 · see citing works
Ziegler, E. J., Fisher, C. J., Sprung, C. L., Straube, R., SADOFF, J. C., Foulke, G. E., Wortel, C. H., Fink, M. P., Dellinger, R. P., Teng, N. N. H., et al. (1991) · New England Journal of Medicine · doi:10.1056/nejm199102143240701 · Cited by 1,618 · see citing works
Bacterial endotoxin: molecular relationships of structure to activity and function
Rietschel, E., Kirikae, T., Schade, F. U., Mamat, U., Schmidt, G., Loppnow, H., Ulmer, A. J., Zähringer, U., Seydel, U., Padova, F. D., et al. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.2.8119492 · Cited by 1,608 · see citing works
Andersson, U., Wang, H., Palmblad, K., Aveberger, A.-C., Bloom, O., Erlandsson-Harris, H., Janson, A., Kokkola, R., Zhang, M., Yang, H., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.4.565 · Cited by 1,401 · see citing works
Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran
Kim, H. M., Park, B. S., Kim, J.-I., Kim, S. E., Lee, J., Oh, S. C., Enkhbayar, P., Matsushima, N., Lee, H., Yoo, O. J., et al. (2007) · Cell · doi:10.1016/j.cell.2007.08.002 · Cited by 1,180 · see citing works
Bacterial lipopolysaccharides and innate immunity
Alexander, C., & Rietschel, E. T. (2001) · Journal of Endotoxin Research · doi:10.1179/096805101101532675 · Cited by 1,173 · see citing works
Recognition of pathogen-associated molecular patterns by TLR family
Akira, S., & Hemmi, H. (2003) · Immunology Letters · doi:10.1016/s0165-2478(02)00228-6 · Cited by 1,139 · see citing works
Fisher, C. J. (1994) · JAMA · doi:10.1001/jama.271.23.1836 · Cited by 1,049 · see citing works
Drotrecogin Alfa (Activated) for Adults with Severe Sepsis and a Low Risk of Death
Abraham, E. H., Laterre, P., Garg, R., Levy, H. A., Talwar, D., Trzaskoma, B. L., François, B., Guy, J. S., Brückmann, M., Réa-Neto, Á., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050935 · Cited by 887 · see citing works
Opal, S. M., Scannon, P. J., Vincent, J., White, M., Carroll, S. F., Palardy, J. E., Parejo, N. A., Pribble, J. P., & Lemke, J. H. (1999) · The Journal of Infectious Diseases · doi:10.1086/315093 · Cited by 609 · see citing works
Agnese, D. M., Calvano, J. E., Hahm, S. J., Coyle, S. M., Corbett, S., Calvano, S. E., & Lowry, S. F. (2002) · The Journal of Infectious Diseases · doi:10.1086/344893 · Cited by 570 · see citing works
A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis*
Rice, T. W., Wheeler, A. P., Bernard, G. R., Vincent, J.-L., Angus, D. C., Aikawa, N., Demeyer, I., Sainati, S., Amlot, N., Cao, C., et al. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181e7c5c9 · Cited by 512 · see citing works
Panacek, E. A., Marshall, J. C., Albertson, T. E., Johnson, D. H., Johnson, S. B., MacArthur, R. D., Miller, M. J., Barchuk, W., Fischkoff, S. A., Kaul, M., et al. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000145229.59014.6c · Cited by 385 · see citing works
Abraham, E. H. (1997) · JAMA · doi:10.1001/jama.1997.03540430043031 · Cited by 377 · see citing works
A second large controlled clinical study of E5, a monoclonal antibody to endotoxin
Bone, R. C., BALK, R. A., Fein, A. M., Perl, T. M., Wenzel, R. P., Reines, H. D., Quenzer, R. W., Iberti, T. J., MacIntyre, N. R., & Schein, R. M. H. (1995) · Critical Care Medicine · doi:10.1097/00003246-199506000-00003 · Cited by 347 · see citing works
Risk and the Efficacy of Antiinflammatory Agents: Retrospective and Confirmatory Studies of Sepsis
Eichacker, P. Q., Parent, C., Kalil, A. C., Esposito, C., Cui, X., Banks, S. M., Gerstenberger, E. P., Fitz, Y., Danner, R. L., & Natanson, C. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200204-302oc · Cited by 340 · see citing works
Self-citationIdentification of pediatric septic shock subclasses based on genome-wide expression profiling
Wong, H. R., Cvijanovich, N. Z., Lin, R., Allen, G. L., Thomas, N. J., Willson, D. F., Freishtat, R. J., ANAS, N. G., Meyer, K., Checchia, P. A., et al. (2009) · BMC Medicine · doi:10.1186/1741-7015-7-34 · Cited by 304 · see citing works
Mullarkey, M. A., Rose, J., Bristol, J., Kawata, T., Kimura, A., Kobayashi, S., Przetak, M. M., Chow, J. C., Gusovsky, F., Christ, W. J., et al. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.044487 · Cited by 292 · see citing works
Inhibition of Toll-like Receptor 4 With Eritoran Attenuates Myocardial Ischemia-Reperfusion Injury
Shimamoto, A., Chong, A. J., Yada, M., Shomura, S., Takayama, H., Fleisig, A. J., Agnew, M. L., Hampton, C. R., Rothnie, C. L., Spring, D. J., et al. (2006) · Circulation · doi:10.1161/circulationaha.105.000901 · Cited by 283 · see citing works
Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4
Roger, T., Froidevaux, C., Roy, D. L., Reymond, M. K., Chanson, A.-L., Mauri, D., Burns, K., Riederer, B. M., Akira, S., & Calandra, T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808146106 · Cited by 267 · see citing works
E5 Murine Monoclonal Antiendotoxin Antibody in Gram-Negative Sepsis A Randomized Controlled Trial
Angus, D. C. (2000) · JAMA · doi:10.1001/jama.283.13.1723 · Cited by 267 · see citing works
Tidswell, M., Tillis, W., LaRosa, S., Lynn, M., Wittek, A., Kao, R., Wheeler, J., Gogate, J., & Opal, S. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181b07b78 · Cited by 230 · see citing works
Pharmacological Inhibition of Endotoxin Responses Is Achieved by Targeting the TLR4 Coreceptor, MD-2
Visintin, A., Halmen, K. A., Latz, E., Monks, B. G., & Golenbock, D. T. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6465 · Cited by 153 · see citing works
Blocking of Responses to Endotoxin by E5564 in Healthy Volunteers with Experimental Endotoxemia
Lynn, M., Rossignol, D. P., Wheeler, J. L., Kao, R., Perdomo, C. A., Noveck, R. J., Vargas, R., D’Angelo, T., Gotzkowsky, S., & McMahon, F. G. (2003) · The Journal of Infectious Diseases · doi:10.1086/367990 · Cited by 150 · see citing works
Anti-inflammatory therapies in sepsis and septic shock
Freeman, B. D., & Natanson, C. (2000) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.9.7.1651 · Cited by 146 · see citing works
Self-citationToll-like Receptor 4 Modulation as a Strategy to Treat Sepsis
Wittebole, X., Castanares‐Zapatero, D., & Laterre, P. (2010) · Mediators of Inflammation · doi:10.1155/2010/568396 · Cited by 141 · see citing works
Minneci, P. C., Deans, K. J., Eichacker, P. Q., & Natanson, C. (2009) · Clinical Microbiology and Infection · doi:10.1111/j.1469-0691.2009.02752.x · Cited by 129 · see citing works
Self-citationPolymorphisms in Toll-like receptor 4 and the systemic inflammatory response syndrome
Child, N. J. A., Yang, I. A., Pulletz, M., de Courcy-Golder, K., ANDREWS, A., Pappachan, J., & Holloway, J. W. (2003) · Biochemical Society Transactions · doi:10.1042/bst0310652 · Cited by 98 · see citing works
Inhibition of Endotoxin Response by Synthetic TLR4 Antagonists
Hawkins, L. D., Christ, W. J., & Rossignol, D. P. (2004) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026043388123 · Cited by 89 · see citing works
Reinhart, K., Glück, T., Ligtenberg, J. J. M., Tschaikowsky, K., Bruining, A., Bakker, J., Opal, S. M., Moldawer, L. L., Axtelle, T., Turner, T., et al. (2004) · Critical Care Medicine · doi:10.1097/01.ccm.0000124870.42312.c4 · Cited by 80 · see citing works
Antagonism of in vivo and ex vivo response to endotoxin by E5564, a synthetic lipid A analogue
Rossignol, D. P., & Lynn, M. (2002) · Journal of Endotoxin Research · doi:10.1179/096805102125001127 · Cited by 77 · see citing works
Physiologic, Biochemical, and Imaging Characterization of Acute Lung Injury in Mice
Zhou, Z., KOZLOWSKI, J. K., & Schuster, D. P. (2005) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200503-343oc · Cited by 75 · see citing works
Savov, J. D., Brass, D. M., Lawson, B. L., McElvania, E., Walker, J. K. L., & Schwartz, D. A. (2005) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00014.2005 · Cited by 73 · see citing works
Rossignol, D. P., Wasan, K. M., Choo, E., Yau, E. H., Wong, N., Rose, J., Moran, J., & Lynn, M. (2004) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.48.9.3233-3240.2004 · Cited by 72 · see citing works
TLR4 antagonists for endotoxemia and beyond.
Rossignol, D. P., & Lynn, M. (2005) · PubMed · Cited by 71 · see citing works
Antagonism of in vivo and ex vivo response to endotoxin by E5564, a synthetic lipid A analogue
Rossignol, D. P., & Lynn, M. (2002) · Journal of Endotoxin Research · doi:10.1177/09680519020080060601 · Cited by 70 · see citing works
Bennett‐Guerrero, E., Grocott, H. P., Levy, J. H., Stierer, K. A., Hogue, C. W. J., Cheung, A. T., Newman, M. F., Carter, A. A., Rossignol, D. P., & Collard, C. D. (2007) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000253501.07183.2a · Cited by 67 · see citing works
Protective Effects of Toll-like Receptor 4 Inhibitor Eritoran on Renal Ischemia-Reperfusion Injury
Liu, M., Gu, M., Xu, D., Lv, Q., Zhang, W., & Wu, Y. (2010) · Transplantation Proceedings · doi:10.1016/j.transproceed.2010.03.133 · Cited by 63 · see citing works
Wong, Y. N., Rossignol, D. P., Rose, J., Kao, R., Carter, A. R., & Lynn, M. (2003) · The Journal of Clinical Pharmacology · doi:10.1177/0091270003254804 · Cited by 54 · see citing works
Phase I study of a murine monoclonal anti-lipid A antibody in bacteremic and nonbacteremic patients
Harkonen, S., Scannon, P. J., Mischak, R. P., S̄pitler, L. E., Foxall, C., Kennedy, D., & Greenberg, R. N. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.5.710 · Cited by 51 · see citing works
Novel therapies for sepsis: antiendotoxin therapies
Manocha, S., Feinstein, D., Kumar, A., & Kumar, A. (2002) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.11.12.1795 · Cited by 49 · see citing works
Once is not enough: clinical trials in sepsis
Sweeney, D. A., Danner, R. L., Eichacker, P. Q., & Natanson, C. (2008) · Intensive Care Medicine · doi:10.1007/s00134-008-1274-6 · Cited by 46 · see citing works
Self-citationInhibition of Corneal Inflammation by the TLR4 Antagonist Eritoran Tetrasodium (E5564)
Sun, Y., & Pearlman, E. M. (2008) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-2628 · Cited by 43 · see citing works
Kitazawa, T., Tsujimoto, T., Kawaratani, H., & Fukui, H. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2009.06145.x · Cited by 40 · see citing works
Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin
Golenbock, D. T., Will, J. A., Raetz, C. R., & Proctor, R. A. (1987) · Infection and Immunity · doi:10.1128/iai.55.10.2471-2476.1987 · Cited by 39 · see citing works
Greenberg, R. N., Wilson, K., Kunz, A. Y., Wedel, N. I., & Gorelick, K. J. (1992) · Critical Care Medicine · doi:10.1097/00003246-199206000-00005 · Cited by 37 · see citing works
Lynn, M., Wong, Y. N., Wheeler, J. L., Kao, R., Perdomo, C. A., Noveck, R. J., Vargas, R., D’Angelo, T., Gotzkowsky, S., McMahon, F. G., et al. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.056531 · Cited by 35 · see citing works
Tracey, K. J., Sf, L., & Cerami, A. (1988) · PubMed · Cited by 35 · see citing works
Kitazawa, T., Tsujimoto, T., Kawaratani, H., & Fukui, H. (2009) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2008.05770.x · Cited by 33 · see citing works
Lipid X protects mice against fatal Escherichia coli infection
Golenbock, D. T., Leggett, J. E., Rasmussen, P., Craig, W. A., Raetz, C. R. H., & Proctor, R. A. (1988) · Infection and Immunity · doi:10.1128/iai.56.4.779-784.1988 · Cited by 32 · see citing works
Solomon, S. B., Cui, X., Gerstenberger, E. P., Danner, R. L., Fitz, Y., Banks, S. M., Natanson, C., & Eichacker, P. Q. (2006) · The Journal of Infectious Diseases · doi:10.1086/500147 · Cited by 29 · see citing works
Self-citationRossignol, D. P., Wong, N., Noveck, R. J., & Lynn, M. (2008) · Innate Immunity · doi:10.1177/1753425908099173 · Cited by 24 · see citing works
Wasan, K. M., Sivak, O., Cote, R. A., MacInnes, A. I., Boulanger, K. D., Lynn, M., Christ, W. J., Hawkins, L. D., & Rossignol, D. P. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.9.2796-2803.2003 · Cited by 14 · see citing works
Barochia, A. V., Cui, X., Natanson, C., & Eichacker, P. Q. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181b77fe3 · Cited by 12 · see citing works
Self-citationActivation of TLR4/NF-κB signaling pathway in early brain injury after subarachnoid hemorrhage
Ma, C., Yin, W.-N., Cai, B., He, M., Wu, J., Wang, J., Zeng, Y., Ding, J., & You, C. (2009) · Neurological Research · doi:10.1179/016164109x12445616596283 · Cited by 11 · see citing works
Kaneko, K., Ueda, R., Kikuchi, K., Sano, Y., & Yoshimura, T. (1999) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(99)00438-7 · Cited by 10 · see citing works
Liang, E., Wong, Y. N., Allen, I. E., Kao, R., Marino, M. T., & DiLea, C. (2003) · The Journal of Clinical Pharmacology · doi:10.1177/0091270003258653 · Cited by 10 · see citing works
Wasan, K. M., Risovic, V., Sivak, O., Lee, S. D., Mason, D. X., Chiklis, G. R., McShane, J., Lynn, M., Wong, N., & Rossignol, D. P. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9428-8 · Cited by 8 · see citing works
LPS binding protein does not participate in the pharmacokinetics of E5564
Kaneko, K., Ueda, R., Kawata, T., Ishizaka, S. T., & Yoshimura, T. (2004) · Journal of Endotoxin Research · doi:10.1177/09680519040100030501 · Cited by 7 · see citing works
Disposition of a synthetic analogue of lipid A (E5564) in rats
Kaneko, K., Ueda, R., Nemoto, H., Iijima, H., & Yoshimura, T. (2003) · Xenobiotica · doi:10.1080/0049825021000058097 · Cited by 7 · see citing works
Ondiveeran, H. K., & Fox‐Robichaud, A. (2004) · PubMed · Cited by 7 · see citing works
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- [59]Opal SM Scannon PJ Vincent JL Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock J Infect Dis 1999 Nov 180 5 1584 9 10515819
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Ramezani, A., & Raj, D. S. (2013) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013080905 · Cited by 753 · see citing works
TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis
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The gut microbiome and liver cancer: mechanisms and clinical translation
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Toll-like receptors activation, signaling, and targeting: an overview
El-Zayat, S. R., Sibaii, H., & Mannaa, F. A. E. (2019) · Bulletin of the National Research Centre/Bulletin of the National Research Center · doi:10.1186/s42269-019-0227-2 · Cited by 560 · see citing works
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Hancock, R. E. W., Nijnik, A., & Philpott, D. J. (2012) · Nature Reviews Microbiology · doi:10.1038/nrmicro2745 · Cited by 542 · see citing works
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Wang, X., Loram, L. C., Ramos, K. M., de Jesus, A. J., Thomas, J., Cheng, K., Reddy, A., Somogyi, A. A., Hutchinson, M. R., Watkins, L. R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200130109 · Cited by 521 · see citing works
Gao, W., Xiong, Y., Li, Q., & Yang, H. Y. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00508 · Cited by 352 · see citing works
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Caputi, V., & Giron, M. C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061689 · Cited by 338 · see citing works
Lai, H., Lin, T., Chen, T.-W., Kuo, Y.-L., Chang, C., Wu, T.-R., Shu, C.-C., Tsai, Y.-H., Swift, S., & Lu, C. (2021) · Gut · doi:10.1136/gutjnl-2020-322599 · Cited by 333 · see citing works
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Extracellular histone release in response to traumatic injury
Kutcher, M., Xu, J., Vilardi, R. F., Ho, C., Esmon, C. T., & Cohen, M. J. M. (2012) · The Journal of Trauma: Injury, Infection, and Critical Care · doi:10.1097/ta.0b013e318270d595 · Cited by 133 · see citing works
Lü, P., Sodhi, C. P., & Hackam, D. J. (2013) · Pathophysiology · doi:10.1016/j.pathophys.2013.11.007 · Cited by 123 · see citing works
Targeting Toll-like receptors with small molecule agents
Wang, X., Smith, C., & Yin, H. H. (2013) · Chemical Society Reviews · doi:10.1039/c3cs60039d · Cited by 117 · see citing works
The innate immune response to allotransplants: mechanisms and therapeutic potentials
Ochando, J., Ordikhani, F., Boros, P., & Jordan, S. (2019) · Cellular and Molecular Immunology · doi:10.1038/s41423-019-0216-2 · Cited by 102 · see citing works
Qiu, P., Cui, X., Barochia, A. V., Li, Y., Natanson, C., & Eichacker, P. Q. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.623125 · Cited by 94 · see citing works
Self-citationHypoxia Exacerbates Inflammatory Acute Lung Injury via the Toll-Like Receptor 4 Signaling Pathway
Wu, G., Xu, G., Chen, D., Gao, W., Xiong, J.-Q., Shen, H., & Gao, Y. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01667 · Cited by 93 · see citing works
Brandão, S. C. S., Ramos, J. D. O. X., Dompieri, L. T., Godoi, E. T. A. M., de Figueiredo, J. L., SARINHO, E. S. C., Chelvanambi, S., & Aikawa, M. (2020) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2020.09.002 · Cited by 93 · see citing works
Toll-like receptor 4 (TLR4) antagonists as potential therapeutics for intestinal inflammation
Tam, J. S. Y., Coller, J. K., Hughes, P. A., Prestidge, C. A., & Bowen, J. M. (2021) · Indian Journal of Gastroenterology · doi:10.1007/s12664-020-01114-y · Cited by 91 · see citing works
Wang, Y., Shan, X., Chen, G., Jiang, L., Wang, Z., Fang, Q., Liu, X., Wang, J., Zhang, Y., Wu, W., et al. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13221 · Cited by 90 · see citing works
Computational Approaches to Toll-Like Receptor 4 Modulation
Billod, J., Lacetera, A., Guzman‐Caldentey, J., & Martín‐Santamaría, S. (2016) · Molecules · doi:10.3390/molecules21080994 · Cited by 88 · see citing works
Gut microbiota, hypertension and chronic kidney disease: Recent advances
Sircana, A., Michieli, F. D., Parente, R., Framarin, L., Leone, N., Berrutti, M., Paschetta, E., Bongiovanni, D., & Musso, G. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.01.013 · Cited by 86 · see citing works
Gao, W., Wang, Y., Xiong, Y., Sun, L., Wang, L., Wang, K., Lu, H. Y., Bao, A., Turvey, S. E., Li, Q., et al. (2018) · Acta Biomaterialia · doi:10.1016/j.actbio.2018.12.046 · Cited by 82 · see citing works
Barker, G., Leeuwenburgh, C., Brusko, T. M., Moldawer, L. L., Reddy, S. T., & Guirgis, F. W. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10081693 · Cited by 81 · see citing works
Lipopolysaccharide lipid A: A promising molecule for new immunity-based therapies and antibiotics
García-Vello, P., Lorenzo, F. D., Zucchetta, D., Zamyatina, A., Castro, C. D., & Molinaro, A. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107970 · Cited by 83 · see citing works
McDonald, K.-A., Huang, H., Tohme, S. T., Loughran, P., Ferrero, K. M., Billiar, T. R., & Tsung, A. (2014) · Molecular Medicine · doi:10.2119/molmed.2014.00076 · Cited by 80 · see citing works
Li, L., Song, A.-X., Yin, J.-Y., Siu, K., Wong, W., & Wu, J. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.02.022 · Cited by 79 · see citing works
Li, Q., Feng, Y., He, W., Wang, L., Wang, R., Dong, L., & Wang, C. (2017) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2017.04.034 · Cited by 78 · see citing works
Monnet, E., Lapeyre, G., van Poelgeest, E. P., Jacqmin, P., de Graaf, K., Reijers, J. A. A., Moerland, M., Burggraaf, J., & de Min, C. (2016) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.522 · Cited by 79 · see citing works
Wiersinga, W. J. (2011) · Current Opinion in Critical Care · doi:10.1097/mcc.0b013e32834a4aeb · Cited by 78 · see citing works
Wang, Y., Shan, X., Dai, Y., Jiang, L., Chen, G., Zhang, Y., Wang, Z., Dong, L., Wu, J., Guo, G., et al. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.222570 · Cited by 77 · see citing works
An update on classification and management of urosepsis
Wagenlehner, F. R. A., Tandoğdu, Z., & Johansen, T. E. B. (2016) · Current Opinion in Urology · doi:10.1097/mou.0000000000000364 · Cited by 77 · see citing works
Wang, X., Grace, P. M., Pham, M. N., Cheng, K., Strand, K. A., Smith, C., Li, J., Watkins, L. R., & Yin, H. H. (2013) · The FASEB Journal · doi:10.1096/fj.12-222992 · Cited by 76 · see citing works
Natural Products with Toll-Like Receptor 4 Antagonist Activity
Molteni, M., Bosi, A., & Rossetti, C. (2018) · International Journal of Inflammation · doi:10.1155/2018/2859135 · Cited by 75 · see citing works
Liu, Z., Chen, L., Yu, P., Zhang, Y., Fang, B., Wu, C., Luo, W., Chen, X., Li, C., & Liang, G. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00316 · Cited by 72 · see citing works
The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury
Zou, S., Jie, H., Han, X., & Wang, J. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110436 · Cited by 71 · see citing works
Anti-inflammatory mechanisms and therapeutic opportunities in myocardial infarct healing
Kempf, T., Zarbock, A., Vestweber, D., & Wollert, K. C. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0847-y · Cited by 71 · see citing works
Identification of sepsis subtypes in critically ill adults using gene expression profiling
Maslove, D. M., Tang, B. M. P., & McLean, A. S. (2012) · Critical Care · doi:10.1186/cc11667 · Cited by 71 · see citing works
New concepts in the pathogenesis, diagnosis and treatment of bacteremia and sepsis
Huttunen, R., & Aittoniemi, J. (2011) · Journal of Infection · doi:10.1016/j.jinf.2011.08.004 · Cited by 70 · see citing works
Myeloid differentiation 2 as a therapeutic target of inflammatory disorders
Park, S. H., Kim, N. D., Jung, J., Lee, C., Han, S., & Kim, Y. S. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.11.001 · Cited by 67 · see citing works
Chen, L., Fu, W., Zheng, L., Wang, Y., & Liang, G. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.01.015 · Cited by 66 · see citing works
Toll-like Receptor 4 in Acute Kidney Injury
Vallés, P. G., Lorenzo, A. F. G., García, R. D., Cacciamani, V. E., Benardón, M. E., & Costantino, V. V. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021415 · Cited by 68 · see citing works
The Central Role of the Inflammatory Response in Understanding the Heterogeneity of Sepsis-3
Ding, R., Meng, Y., & Ma, X. (2018) · BioMed Research International · doi:10.1155/2018/5086516 · Cited by 64 · see citing works
Zhu, Z., Rahman, Z.-U., Aamir, M., Shah, S. Z. A., Hamid, S., Bilawal, A., Li, S., & Ishfaq, M. (2023) · RSC Advances · doi:10.1039/d2ra06178c · Cited by 63 · see citing works
Artner, D., Oblak, A., Ittig, S., Gárate, J. A., Horvat, S., Arrieumerlou, C., Hofinger, A., Oostenbrink, C., Jerala, R., Kosma, P., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb4003199 · Cited by 62 · see citing works
Pattern recognition receptors as potential drug targets in inflammatory disorders
McKernan, D. P. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.09.001 · Cited by 62 · see citing works
Biology and Metabolism of Sepsis: Innate Immunity, Bioenergetics, and Autophagy
Lewis, A., Billiar, T. R., & Rosengart, M. R. (2016) · Surgical Infections · doi:10.1089/sur.2015.262 · Cited by 62 · see citing works
Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments
Liu, Z., Yang, M., Yu, K., Lian, Z., & Deng, S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.989664 · Cited by 58 · see citing works
Oblak, A., & Jerala, R. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.06.034 · Cited by 55 · see citing works
Progress in the synthesis and biological evaluation of lipid A and its derivatives
Gao, J., & Guo, Z. (2017) · Medicinal Research Reviews · doi:10.1002/med.21447 · Cited by 50 · see citing works
Xu, M.-J., Liu, B.-J., Wang, C.-L., Wang, G., Tian, Y., Wang, S., Jun, L., Li, P.-Y., Zhang, R., Dong, W., et al. (2017) · International Immunopharmacology · doi:10.1016/j.intimp.2017.08.023 · Cited by 50 · see citing works
Chen, L., Jin, Y., Chen, H., Sun, C., Fu, W., Zheng, L., Lu, M., Chen, P., Chen, G., Zhang, Y., et al. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.11.066 · Cited by 48 · see citing works
Xiong, Y., Gao, W., Xia, F., Sun, Y., Sun, L., Wang, X., Ben, S., Turvey, S. E., Yang, H. Y., & Li, Q. (2018) · Advanced Healthcare Materials · doi:10.1002/adhm.201800510 · Cited by 48 · see citing works
Švajger, U., Brus, B., Turk, S., Sova, M., Hodnik, V., Anderluh, G., & Gobec, S. (2013) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2013.10.019 · Cited by 46 · see citing works
Inhibition of TLR4 signalling to dampen joint inflammation in osteoarthritis
Bartels, Y. L., van Lent, P. L. E. M., van der Kraan, P. M., Blom, A. B., Bonger, K. M., & van den Bosch, M. H. J. (2023) · Lara D. Veeken · doi:10.1093/rheumatology/kead493 · Cited by 46 · see citing works
Drugs to cure avian influenza infection – multiple ways to prevent cell death
Yuan, S. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.367 · Cited by 46 · see citing works
Kuang, Q.-X., Lei, L.-R., Li, Q., Peng, W., Wang, Y., Dai, Y., Wang, D., Gu, Y., Deng, Y., & Guo, D. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.881182 · Cited by 44 · see citing works
Ko, C., Zang, S., Zhou, Y., Zhong, Z., & Yang, C. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01582-8 · Cited by 44 · see citing works
A Key Role for the Endothelium in NOD1 Mediated Vascular Inflammation: Comparison to TLR4 Responses
Gatheral, T. L., Reed, D. M., Moreno, L., Gough, P. J., Votta, B. J., Sehon, C. A., Rickard, D. J., Bertin, J., Lim, E. K. S., Nicholson, A. G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042386 · Cited by 44 · see citing works
Sepsis Pathophysiology and Anesthetic Consideration
Yuki, K., & Murakami, N. (2015) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/1871529x15666150108114810 · Cited by 42 · see citing works
Menghini, R., Campia, U., Tesauro, M., Marino, A., Rovella, V., Rodia, G., Schinzari, F., Tolusso, B., Daniele, N. D., Federici, M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0099053 · Cited by 42 · see citing works
Yahaya, M. A. F., Bakar, A. R. A., Stanslas, J., Nordin, N. N. M., Zainol, M., & Mehat, M. Z. (2021) · BMC Biotechnology · doi:10.1186/s12896-021-00697-4 · Cited by 40 · see citing works
Iqubal, A., Syed, M. A., Najmi, A. K., Azam, F., Barreto, G. E., Iqubal, M. K., Ali, J., & Haque, S. E. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113464 · Cited by 38 · see citing works
Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics
Wang, Y., Zhang, H., & Miao, C. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-07714-w · Cited by 41 · see citing works
Molecular simplification of lipid A structure: TLR4-modulating cationic and anionic amphiphiles
Calabrese, V., Cighetti, R., & Peri, F. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.05.011 · Cited by 37 · see citing works
Bolstering Immunity through Pattern Recognition Receptors: A Unique Approach to Control Tuberculosis
Pahari, S., Kaur, G., Aqdas, M., Negi, S., Chatterjee, D., Bashir, H., Singh, S., & Agrewala, J. N. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00906 · Cited by 37 · see citing works
Yuan, F., Chen, Y., Zhao, Y., Liu, Z., Nan, C., Zheng, B., Liu, X., & Chen, X. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28410 · Cited by 37 · see citing works
Fang, H., Jiang, W., Jin, C. S., Lu, Y., Liu, A., Kan, L., & Dahmen, U. (2015) · Journal of Immunology Research · doi:10.1155/2015/187048 · Cited by 36 · see citing works
Tamada, K., Nakajima, S., Ogawa, N., Inada, M., Shibasaki, H., Sato, A., Takasawa, R., Yoshimori, A., Suzuki, Y., Watanabe, N., et al. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.01.136 · Cited by 36 · see citing works
Dwyer, G. K., & Turnquist, H. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.611910 · Cited by 34 · see citing works
Vizantin Inhibits Endotoxin-Mediated Immune Responses via the TLR 4/MD-2 Complex
Oda, M., Yamamoto, H., Shibutani, M., Nakano, M., Yabiku, K., Tarui, T., Kameyama, N., Shirakawa, D., Obayashi, S., Watanabe, N., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401796 · Cited by 32 · see citing works
A Purified Capsular Polysaccharide Markedly Inhibits Inflammatory Response during Endotoxic Shock
Piccioni, M., Monari, C., Kenno, S., Pericolini, E., Gabrielli, E., Pietrella, D., Perito, S., Bistoni, F., Kozel, T. R., & Vecchiarelli, A. (2012) · Infection and Immunity · doi:10.1128/iai.00553-12 · Cited by 31 · see citing works
Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma
Korff, S., Loughran, P., Cai, C., Lee, Y. S., Scott, M. J., & Billiar, T. R. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.03.023 · Cited by 30 · see citing works
Stem Cell-Induced Inflammation in Cholesteatoma Is Inhibited by the TLR4 Antagonist LPS-RS
Schürmann, M., Greiner, J. F. W., Volland-Thurn, V., Oppel, F., Kaltschmidt, C., Sudhoff, H. H., & Kaltschmidt, B. (2020) · Cells · doi:10.3390/cells9010199 · Cited by 29 · see citing works
Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics
Bae, S., Jo, Y., Cho, M. K., Jin, J.-S., Kim, J., Shim, J., Kim, Y. H., Park, J.-K., Ryu, D., Lee, H. J., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.942368 · Cited by 28 · see citing works
Immunomodulatory approaches for prevention and treatment of infectious diseases
Nijnik, A. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.06.011 · Cited by 28 · see citing works
Exploring the Binding Proteins of Glycolipids with Bifunctional Chemical Probes
Liu, X., Dong, T., Zhou, Y., Huang, N., & Lei, X. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201608827 · Cited by 28 · see citing works
Zhang, Y., & Igwe, O. J. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.11.012 · Cited by 26 · see citing works
Acute kidney injury: a conspiracy of toll-like receptor 4 on endothelia, leukocytes, and tubules
Lu, C. Y., Winterberg, P. D., Chen, J., & Hartono, J. R. (2011) · Pediatric Nephrology · doi:10.1007/s00467-011-2029-0 · Cited by 26 · see citing works
Eslami, M., Nezafat, N., Negahdaripour, M., & Ghasemi, Y. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2018.1564701 · Cited by 27 · see citing works
Effect of acute TLR4 inhibition on insulin resistance in humans
Liang, H., Sathavarodom, N., Colmenares, C., Gelfond, J., Espinoza, S. E., Ganapathy, V., & Musi, N. (2022) · Journal of Clinical Investigation · doi:10.1172/jci162291 · Cited by 28 · see citing works
Chen, Y., Shiau, A., Wang, S., Yang, J., Chang, S.-J., Wu, C., & Wu, T.-S. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1301931 · Cited by 24 · see citing works
Key residues in TLR4-MD2 tetramer formation identified by free energy simulations
Tafazzol, A., & Duan, Y. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007228 · Cited by 24 · see citing works
Tume, R., Sherbiny, S. E., Bono, R., Gautier, T., de Barros, J.-P. P., & Meroño, T. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1588129 · Cited by 23 · see citing works
Evolving Paradigms in Sepsis Management: A Narrative Review
Kim, M., Choi, E.-J., & Choi, E.-J. (2024) · Cells · doi:10.3390/cells13141172 · Cited by 23 · see citing works
Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma
Fatima, N., Akhtar, T., & Sheikh, N. (2017) · Canadian Journal of Gastroenterology and Hepatology · doi:10.1155/2017/6238106 · Cited by 22 · see citing works
Sepsis: the evolution of molecular pathogenesis concepts and clinical management
Feng, Z., Wang, L., Yang, J. L., Li, T., Liao, X., Kang, Y. M., Xiao, F., & Zhang, W. (2025) · MedComm · doi:10.1002/mco2.70109 · Cited by 21 · see citing works
Toll-Like Receptor 4 Plays a Central Role in Cardiac Dysfunction During Trauma Hemorrhage Shock
Zhang, X., Chen, L., Gao, M., Cao, X.-Y., Ha, T., Kalbfleisch, J. H., Williams, D. L., Li, C., & Kao, R. L. (2014) · Shock · doi:10.1097/shk.0000000000000155 · Cited by 20 · see citing works
Merk, D., Cox, F. F., Jakobs, P., Prömel, S., Altschmied, J., & Haendeler, J. (2024) · Antioxidants · doi:10.3390/antiox13040443 · Cited by 19 · see citing works
Novel Synthetic Toll-Like Receptor 4/MD2 Ligands Attenuate Sterile Inflammation
Hayashi, T., Crain, B., Yao, S., Caneda, C. D., Cottam, H. B., Chan, M., Corr, M., & Carson, D. A. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.214312 · Cited by 19 · see citing works
- Authors
- Barochia, A., Solomon, S., Cui, X., Natanson, C., & Eichacker, P. Q.
- Affiliations
- National Institutes of Health (US)
- Venue
- Expert Opinion on Drug Metabolism & Toxicology
- Publisher
- Informa Healthcare
- Published
- 2011-02-17
- Volume
- 7
- Issue
- 4
- Pages
- 479-494
- ISSN
- 1742-5255 (ISSN-L)
- 1744-7607
- PMC
- PMC3065179
- OpenAlex
- W2161681729
- Cited by
- 169
- References
- 66
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 13 · 2016: 12 · 2015: 8 · 2014: 10 · 2013: 14 · 2012: 13
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Expert Opinion on Drug Metabolism & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99CL999999)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- sepsis, lipopolysaccharide, TLR4, anti-inflammatory therapy, pharmacokinetics, pharmacodynamics, drug safety, sepsis mortality, inflammatory mediator release
- MeSH terms
- Animals, Anti-Inflammatory Agents, Clinical Trials as Topic, Disaccharides, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Humans, Lipopolysaccharides, Sugar Phosphates, Sepsis, Toll-Like Receptor 4, Drug-Related Side Effects and Adverse Reactions
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