complement inactivating agents

Summary

Summary: Compounds that negatively regulate the cascade process of COMPLEMENT ACTIVATION. Uncontrolled complement activation and resulting cell lysis is potentially dangerous for the host.

Top Publications

  1. Maurer M, Magerl M. Long-term prophylaxis of hereditary angioedema with androgen derivates: a critical appraisal and potential alternatives. J Dtsch Dermatol Ges. 2011;9:99-107 pubmed publisher
    ..Patients might benefit from a dose reduction or the withdrawal of androgen prophylaxis and attacks can be controlled with demand-oriented acute treatment using C1-INH or icatibant. ..
  2. Craig T, Levy R, Wasserman R, Bewtra A, Hurewitz D, Obtułowicz K, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124:801-8 pubmed publisher
    ..C1 esterase inhibitor concentrate given intravenously at a dose of 20 U/kg is an effective and safe treatment for acute abdominal and facial attacks in patients with hereditary angioedema, with a rapid onset of relief. ..
  3. Zuraw B. Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359:1027-36 pubmed publisher
  4. Zuraw B, Busse P, White M, Jacobs J, Lumry W, Baker J, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363:513-22 pubmed publisher
    ..When used for prophylaxis, nanofiltered C1 inhibitor concentrate reduced the frequency of acute attacks. (Funded by Lev Pharmaceuticals; ClinicalTrials.gov numbers, NCT00289211, NCT01005888, NCT00438815, and NCT00462709.) ..
  5. Hammel M, Sfyroera G, Pyrpassopoulos S, Ricklin D, Ramyar K, Pop M, et al. Characterization of Ehp, a secreted complement inhibitory protein from Staphylococcus aureus. J Biol Chem. 2007;282:30051-61 pubmed
    ..Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein. ..
  6. Trendelenburg M, Theroux P, Stebbins A, Granger C, Armstrong P, Pfisterer M. Influence of functional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Eur Heart J. 2010;31:1181-7 pubmed publisher
    ..This unique finding suggests that a component of the innate immune system affects mortality in STEMI patients undergoing primary PCI. clinicaltrials.gov, Identifier: NCT00091637. ..
  7. Testa L, van Gaal W, Bhindi R, Biondi Zoccai G, Abbate A, Agostoni P, et al. Pexelizumab in ischemic heart disease: a systematic review and meta-analysis on 15,196 patients. J Thorac Cardiovasc Surg. 2008;136:884-93 pubmed publisher
    ..However, pexelizumab reduces the risk of death in patients undergoing coronary artery bypass grafting. ..
  8. Mao Y, Yu Q, Zheng X, Liu K, Liang W, Wang Y, et al. Pre-treatment with Cobra venom factor alleviates acute lung injury induced by intestinal ischemia-reperfusion in rats. Eur Rev Med Pharmacol Sci. 2013;17:2207-17 pubmed
    ..CVF might be an efficient reagent for preventing the IIR injuries in clinical condition. ..
  9. Danobeitia J, Ziemelis M, Ma X, Zitur L, Zens T, Chlebeck P, et al. Complement inhibition attenuates acute kidney injury after ischemia-reperfusion and limits progression to renal fibrosis in mice. PLoS ONE. 2017;12:e0183701 pubmed publisher
    ..We conclude that early complement blockade in the context of IRI constitutes an effective strategy in the prevention of fibrosis after ischemic acute kidney injury. ..

More Information

Publications60

  1. Greenbaum L, Fila M, Ardissino G, Al Akash S, Evans J, Henning P, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016;89:701-11 pubmed publisher
    ..Thus, our findings establish the efficacy and safety of eculizumab for pediatric patients with aHUS and are consistent with proposed immediate eculizumab initiation following diagnosis in children. ..
  2. Moghimi S, Farhangrazi Z. Nanomedicine and the complement paradigm. Nanomedicine. 2013;9:458-60 pubmed publisher
    ..In this paper, idiosyncratic reactions based on complement activation are discussed in the context of newly available complement inhibitors. ..
  3. Mika A, Reynolds S, Pickering D, McMillan D, Sriprakash K, Kemp D, et al. Complement inhibitors from scabies mites promote streptococcal growth--a novel mechanism in infected epidermis?. PLoS Negl Trop Dis. 2012;6:e1563 pubmed publisher
    ..Treatment of scabies decreases the prevalence of infections by bacteria. This study aims to identify the molecular mechanisms underlying the link between scabies and GAS infections...
  4. Lane C, Grant J, Dougherty D. Life with hereditary angioedema: then and now. Postgrad Med. 2012;124:144-51 pubmed publisher
    ..Additionally, we will emphasize the humanistic impact of the disorder by describing the real-life experiences of a contemporary family who has documented their experience with HAE across 7 generations. ..
  5. Seregin S, Hartman Z, Appledorn D, Godbehere S, Jiang H, Frank M, et al. Novel adenovirus vectors 'capsid-displaying' a human complement inhibitor. J Innate Immun. 2010;2:353-9 pubmed publisher
    ..In summary, our work has shown that a novel COMPinh-displaying Ad5 has the potential for broadening the safe use of Ad vectors in future human applications. ..
  6. Bygum A, Andersen K, Mikkelsen C. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol. 2009;19:147-51 pubmed publisher
    ..Self-administration of C1-INH improved QOL on both physical and psychological parameters. Patients were able to resume a normal life without restrictions caused by the condition. ..
  7. Hawksworth O, Li X, Coulthard L, Wolvetang E, Woodruff T. New concepts on the therapeutic control of complement anaphylatoxin receptors. Mol Immunol. 2017;89:36-43 pubmed publisher
    ..This review provides an update on the growing arsenal of drugs now available to target C5, and C5a and C3a receptor signaling, and discusses their utility in both clinical and pre-clinical development. ..
  8. Risitano A. Paroxysmal nocturnal hemoglobinuria and the complement system: recent insights and novel anticomplement strategies. Adv Exp Med Biol. 2013;735:155-72 pubmed
  9. Lim W. Complement and the antiphospholipid syndrome. Curr Opin Hematol. 2011;18:361-5 pubmed publisher
    ..Complement inhibition may provide a novel upstream treatment option for patients with APS compared with the current standard treatment of anticoagulation. ..
  10. Yang K, DeAngelis R, Reed J, Ricklin D, Lambris J. Complement in action: an analysis of patent trends from 1976 through 2011. Adv Exp Med Biol. 2013;735:301-13 pubmed
    ..All of the patents discussed in this chapter, as well as those from other databases, are available from our newly constructed complement patent database: www.innateimmunity.us/patent. ..
  11. Morgan B. Hereditary angioedema--therapies old and new. N Engl J Med. 2010;363:581-3 pubmed publisher
  12. Zhang T, Chen D. Anticomplementary principles of a Chinese multiherb remedy for the treatment and prevention of SARS. J Ethnopharmacol. 2008;117:351-61 pubmed publisher
    ..Luteolin could be a potential anticomplementary agent. ..
  13. Thurman J. Complement in kidney disease: core curriculum 2015. Am J Kidney Dis. 2015;65:156-68 pubmed publisher
  14. Girardi G. Guilty as charged: all available evidence implicates complement's role in fetal demise. Am J Reprod Immunol. 2008;59:183-92 pubmed publisher
  15. Farkas H, Varga L, Széplaki G, Visy B, Harmat G, Bowen T. Management of hereditary angioedema in pediatric patients. Pediatrics. 2007;120:e713-22 pubmed
    ..Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood. ..
  16. Proctor L, Strachan A, Woodruff T, Mahadevan I, Williams H, Shiels I, et al. Complement inhibitors selectively attenuate injury following administration of cobra venom factor to rats. Int Immunopharmacol. 2006;6:1224-32 pubmed
  17. Riedl M, Hurewitz D, Levy R, Busse P, Fitts D, Kalfus I. Nanofiltered C1 esterase inhibitor (human) for the treatment of acute attacks of hereditary angioedema: an open-label trial. Ann Allergy Asthma Immunol. 2012;108:49-53 pubmed publisher
    ..75 hour. C1 INH-nf was safe and well tolerated. This open-label study demonstrates the efficacy and safety of C1 INH-nf for short-term treatment of HAE attacks. clinicaltrials.gov Identifier: NCT00438815. ..
  18. Erkan D, Salmon J. The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome. Turk J Haematol. 2016;33:1-7 pubmed publisher
    ..Halen devam etmekte olan ve gelecekte yap?lacak klinik çal??malar, aPL-pozitif hastalar?n yönetiminde kompleman inhibitörlerinin rolünü belirlemede yard?mc? olacakt?r. ..
  19. Jiang L, Wang Z, Zhu H, Di H, Li H, Zhang Y, et al. Beneficial effect of Eucommia polysaccharides on systemic lupus erythematosus-like syndrome induced by Campylobacter jejuni in BALB/c mice. Inflammation. 2011;34:402-11 pubmed publisher
    ..These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice...
  20. Herbert A, Soares D, Pangburn M, Barlow P. Disease-associated sequence variations in factor H: a structural biology approach. Adv Exp Med Biol. 2006;586:313-27 pubmed
  21. Salmon J, Girardi G. Theodore E. Woodward Award: antiphospholipid syndrome revisited: a disorder initiated by inflammation. Trans Am Clin Climatol Assoc. 2007;118:99-114 pubmed
    ..Our studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and emphasize the importance of developing and testing targeted complement inhibitory therapy for patients with APS. ..
  22. Katschke K, Helmy K, Steffek M, Xi H, Yin J, Lee W, et al. A novel inhibitor of the alternative pathway of complement reverses inflammation and bone destruction in experimental arthritis. J Exp Med. 2007;204:1319-25 pubmed
    ..The extracellular domain of CRIg thus provides a novel tool to study the effects of inhibiting the AP of complement in established disease and constitutes a promising therapeutic with selectivity for a single complement pathway. ..
  23. Serhan C. Novel chemical mediators in the resolution of inflammation: resolvins and protectins. Anesthesiol Clin. 2006;24:341-64 pubmed
    ..In view of the essential roles of DHA and EPA in human biology and medicine uncovered to date, the physiologic relevance of the resolvins and protectins is likely to extend beyond our current appreciation. ..
  24. De Silva R, Vuylsteke A, Fritchley S, Trull A, Dunning J, Wallwork J. APT070 inhibits complement activation during in vitro cardiopulmonary bypass. Eur J Cardiothorac Surg. 2006;30:72-6 pubmed
    ..04 at 90 min). APT070 significantly inhibits complement and neutrophil activation. This result may have considerable implications, especially if it can be shown to decrease the inflammatory sequelae of CPB. ..
  25. Begieneman M, Kubat B, Ulrich M, Hahn N, Stumpf Stolker Y, Tempelaars M, et al. Prolonged C1 inhibitor administration improves local healing of burn wounds and reduces myocardial inflammation in a rat burn wound model. J Burn Care Res. 2012;33:544-51 pubmed publisher
    ..Therefore, C1inh might be a possible therapeutic intervention for burn wound patients. ..
  26. Plosker G. Recombinant human c1 inhibitor (conestat alfa): in the treatment of angioedema attacks in hereditary angioedema. BioDrugs. 2012;26:315-23 pubmed publisher
    ..In the two randomized controlled trials, headache and vertigo were the only adverse events deemed to be related to study treatment. ..
  27. Ali Z, Khan S, Ferreira D, Khan I. Podocarpaside, a triterpenoid possessing a new backbone from Actaea podocarpa. Org Lett. 2006;8:5529-32 pubmed
    ..Podocarpaside belongs to a new class of triterpenoids, for which the name "ranunculane" is proposed. Compound 1 possesses anticomplement activity. [structure: see text]...
  28. Roumenina L, Loirat C, Dragon Durey M, Halbwachs Mecarelli L, Sautes Fridman C, Fremeaux Bacchi V. Alternative complement pathway assessment in patients with atypical HUS. J Immunol Methods. 2011;365:8-26 pubmed publisher
    ..Finally, we will discuss how the therapy of aHUS patients can be modified according to the functional consequences of each particular genetic defect. ..
  29. Rohrer B, Long Q, Coughlin B, Renner B, Huang Y, Kunchithapautham K, et al. A targeted inhibitor of the complement alternative pathway reduces RPE injury and angiogenesis in models of age-related macular degeneration. Adv Exp Med Biol. 2010;703:137-49 pubmed publisher
    ..In both the in vivo and in vitro paradigm of RPE damage, a model requiring molecular events known to be involved in AMD, complement-dependent VEGF production, was confirmed. These data may open new avenues for AMD treatment strategies. ..
  30. Karagianni N, Adamis A. The case for complement and inflammation in AMD: open questions. Adv Exp Med Biol. 2010;703:1-7 pubmed publisher
    ..Answering these and other questions will provide investigators with a clear framework with which to evaluate progress in the field and help guide the development of future clinical therapeutics. ..
  31. Gitiaux C, Krug P, Grevent D, Kossorotoff M, Poncet S, Eisermann M, et al. Brain magnetic resonance imaging pattern and outcome in children with haemolytic-uraemic syndrome and neurological impairment treated with eculizumab. Dev Med Child Neurol. 2013;55:758-65 pubmed publisher
    ..These results call for further evaluation of the potential role of eculizumab in the choice of treatment for severe D+HUS, particularly in the case of early neurological signs. ..
  32. Sommer W, Tudorache I, Kuhn C, Avsar M, Salman J, Ius F, et al. C1-esterase-inhibitor for primary graft dysfunction in lung transplantation. Transplantation. 2014;97:1185-91 pubmed publisher
    ..Although survival in the C1-INH treated patients was lower than in the remaining collective, it was as good or better, compared with the PGD3 group and as what is internationally regarded as reasonable after LTX. ..
  33. Tabib A, Karbian N, Mevorach D. Demyelination, strokes, and eculizumab: Lessons from the congenital CD59 gene mutations. Mol Immunol. 2017;89:69-72 pubmed publisher
  34. Wakisaka M, Shuto M, Abe H, Tajima M, Shiroshita H, Bandoh T, et al. Computed tomography of the gastrointestinal manifestation of hereditary angioedema. Radiat Med. 2008;26:618-21 pubmed publisher
    ..The importance of considering this condition in patients presenting such CT findings correlated with the appropriate history is discussed. ..
  35. Schneider L, Hurewitz D, Wasserman R, Obtulowicz K, Machnig T, Moldovan D, et al. C1-INH concentrate for treatment of acute hereditary angioedema: a pediatric cohort from the I.M.P.A.C.T. studies. Pediatr Allergy Immunol. 2013;24:54-60 pubmed publisher
    ..Of 4 treatment-emergent adverse events in both studies, only 2 were considered related to treatment. Study results showed that outcomes with pdC1-INH treatment of HAE in pediatric patients are comparable with outcomes in adults. ..
  36. Schmidt C, Harder M, Nichols E, Hebecker M, Anliker M, Höchsmann B, et al. Selectivity of C3-opsonin targeted complement inhibitors: A distinct advantage in the protection of erythrocytes from paroxysmal nocturnal hemoglobinuria patients. Immunobiology. 2016;221:503-11 pubmed publisher
    ..Thus, the molecular design of each C3-opsonin targeted complement inhibitor determines its potency in respect to the nature of the activator/surface providing potential functionality in PNH. ..
  37. Prematta M, Bewtra A, Levy R, Wasserman R, Jacobson K, Machnig T, et al. Per-attack reporting of prodromal symptoms concurrent with C1-inhibitor treatment of hereditary angioedema attacks. Adv Ther. 2012;29:913-22 pubmed publisher
    ..Additional well-designed prospective studies are clearly needed to continue investigating the potential clinical relevance of prodromes. ..
  38. Bernstein J, Moellman J. Progress in the emergency management of hereditary angioedema: focus on new treatment options in the United States. Postgrad Med. 2012;124:91-100 pubmed publisher
    ..For the first time, US physicians have rapid-acting and highly effective treatments for managing acute HAE attacks. ..
  39. Schmitz Valckenberg S, Mossner A, Fleckenstein M, Wiedemann P, Holz F. [Therapy approaches for geographic atrophy]. Ophthalmologe. 2010;107:1016-9 pubmed publisher
    ..Until efficacy and safety is demonstrated, aids for poor vision and further rehabilitative measures remain essential for patients with advanced dry AMD. ..
  40. Ali Z, Khan S, Khan I. New cycloartane-type triterpene arabinosides from the roots of Actaea podocarpa and their biological study. Planta Med. 2007;73:699-703 pubmed
    ..They were found inactive in the tested assays, except for podocarpaside I (2), which showed moderate anticomplement activity with an IC(50) value of 250 microM...
  41. Kavanagh D, Goodship T. Atypical hemolytic uremic syndrome. Curr Opin Hematol. 2010;17:432-8 pubmed publisher
    ..Although early reports of the efficacy of the complement inhibitor eculizumab are promising, the outcome of a recent clinical trial is awaited. ..
  42. Kuno N, Fujii S. Dry age-related macular degeneration: recent progress of therapeutic approaches. Curr Mol Pharmacol. 2011;4:196-232 pubmed
    ..In this article, the progress of therapeutic approaches for dry AMD is reviewed. ..
  43. Van Sickels N, Hunsaker R, Van Sickels J. Hereditary angioedema: treatment, management, and precautions in patients presenting for dental care. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2010;109:168-72 pubmed publisher
    ..This paper reviews this entity and presents 2 patients who presented for acute care with dental/oral surgical complaints. ..
  44. Leendertse M, Willems R, Flierman R, de Vos A, Bonten M, van der Poll T. The complement system facilitates clearance of Enterococcus faecium during murine peritonitis. J Infect Dis. 2010;201:544-52 pubmed publisher
    ..Complement deficiency severely hampers the clearance of E. faecium peritonitis and subsequent systemic infection. ..
  45. Yang L, Sun M, Gailani D, Rezaie A. Characterization of a heparin-binding site on the catalytic domain of factor XIa: mechanism of heparin acceleration of factor XIa inhibition by the serpins antithrombin and C1-inhibitor. Biochemistry. 2009;48:1517-24 pubmed publisher
  46. Park B, Min B, Oh S, Kim J, Bae K, Lee H. Isolation of flavonoids, a biscoumarin and an amide from the flower buds of Daphne genkwa and the evaluation of their anti-complement activity. Phytother Res. 2006;20:610-3 pubmed
    ..Among the compounds, daphnoretin (9) exhibited significant anti-complement activity with an IC(50) value of 11.4 microm, whereas the other compounds were not active in the assay...
  47. Kim S, Kim J, Lee J, Cho S, Kang H, Kim K, et al. Intravitreal human complement factor H in a rat model of laser-induced choroidal neovascularisation. Br J Ophthalmol. 2013;97:367-70 pubmed publisher
    ..Human CFH may be a feasible treatment for CNV associated with age-related macular degeneration or other causes. ..
  48. Zhang J, Hu W, Xing W, You T, Xu J, Qin X, et al. The protective role of CD59 and pathogenic role of complement in hepatic ischemia and reperfusion injury. Am J Pathol. 2011;179:2876-84 pubmed publisher
    ..Taken together, these results highlight the protective role of CD59 and pathogenic role of complement, including MAC, in the pathogenesis of hepatic IRI. ..
  49. Fain O. [Hereditary angioedema C1 inhibitor deficiency]. Rev Prat. 2007;57:591 pubmed
  50. Funayama H, Huang L, Sato T, Ohtaki Y, Asada Y, Yokochi T, et al. Pharmacological characterization of anaphylaxis-like shock responses induced in mice by mannan and lipopolysaccharide. Int Immunopharmacol. 2009;9:1518-24 pubmed publisher
    ..Man-ALS and LPS-ALS may therefore serve as models for diseases involving augmentation by multiple or mixed infections. ..
  51. Kreuz W, Martinez Saguer I, Aygören Pürsün E, Rusicke E, Heller C, Klingebiel T. C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis. Transfusion. 2009;49:1987-95 pubmed publisher