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16-September-2008 16:15:12 - Abatacept Abatacept Systematic IUPAC name Unable to be assigned Identifiers CAS number ? ATC code L04AA24 PubChem ? Chemical data Formula ? Mol. mass ? Pharmacokinetic data Bioavailability ? Metabolism ? Half life ? Excretion ? Therapeutic considerations Pregnancy cat. C U.S. Legal status POM UK, ℞-only U.S. Routes Intravenous Abatacept marketed as Orencia is a fusion protein composed of an immunoglobulin fused to the extracellular domain of CTLA-4, a molecule capable of binding B7. Abatacept is a selective costimulation modulator as it inhibits the costimulation of T cells. It was developed by Bristol-Myers-Squibb and is licensed in the United States for the treatment of rheumatoid arthritis in the case of inadequate response to anti-TNFα therapy. Contents 1 Mechanism of action 2 Indications 3 Structure 4 Similar agents 5 References 6 External links Mechanism of action Ordinarily, full T cell activation requires 1 binding of the T cell receptor to the antigen-MHC complex on the antigen presenting cell APC and 2 a costimulatory signal provided by the binding of the T cell's CD28 protein to the B7 protein on the APC. Abatacept, which contains a high-affinity binding site for B7, works by binding to the B7 protein on APCs and preventing them from delivering the costimulatory signal to T cells, thus preventing the full activation of T cells.12 Abatacept is the basis for the second-generation belatacept currently being tested in clinical trials. In organ transplantation, it is intended to provide extended graft survival while limiting the toxicity generated by standard immune-suppressing regimens such as calcineurin inhibitors eg, ciclosporin. Indications Abatacept is currently approved for use in rheumatoid arthritis patients who have had an inadequate response to one or more DMARDs.3 It is useful in delaying the progression of structural damage and reducing symptoms of rheumatoid arthritis. However, it should not be used in combination with anakinra or TNF antagonists.4 It is also likely to be beneficial in the treatment of psoriasis and in organ transplantation.citation needed Abatacept is currently in trial5 for the treatment of patients suffering moderate to severe active ulcerative colitis, where response to standard treatment has failed to bring about remission. Abatacept is also currently in trial6 for the treatment of Type 1 Diabetes. In diabetic patients in the honeymoon phase of the disease, Abatacept may protect surviving beta cells from autoimmune attack. Structure Abatacept is a fusion protein composed of the extracellular domain of CTLA-4 with the hinge, CH2, and CH3 domains of IgG1.4 Similar agents Belatacept References ^ ABATACEPT BELATACEPT: the CTLA-4-Igs. Healthvalue.net. Retrieved on 2007-05-25. ^ Dall'Era M, Davis J 2004. CTLA4Ig: a novel inhibitor of co-stimulation. Lupus 13 5: 372-376. doi:10.1191/0961203303lu1029oa. PMID 15230295. ^ Bristol-Myers Squibb March 13, 2007. ORENCIA labelPDF 110 KiB. United States Food and Drug Administration. Retrieved on 2007-05-25. ^ a b Moreland L, Bate G, Kirkpatrick P 2006. Abatacept. Nature Reviews Drug Discovery 5: 185-186. doi:10.1038/nrd1989. PMID 16557658. ^ A Study of Abatacept in Patients With Active Ulcerative Colitis. ClinicalTrials.gov. United States National Institutes of Health May 11, 2007. Retrieved on 2007-05-25. ClinicalTrials.gov Identifier NCT00410410. ^ CTLA-4 Ig Abatacept in Recent Onset Diabetes. diabetestrialnet.org. TrialNet. Retrieved on 2008-08-08. diabetestrialnet.org. External links Orencia Official Site v d e Immunomodulators - Immunosuppressants - Immunosuppressive drugs L04 Extracellular Antibodies CD3 Muromonab-CD3, Teplizumab, Visilizumab · CD4 Keliximab, Zanolimumab · CD11a Efalizumab · CD20 Ocrelizumab, Pascolizumab · CD23 Lumiliximab · IL-2/CD25 Basiliximab, Daclizumab, Inolimomab · CD40 Teneliximab · CD62L/L-selectin Aselizumab · CD147/Basigin Gavilimomab, Ziralimumab · CD154 Ruplizumab BLyS Belimumab · Complement component 5 Eculizumab · CTLA-4 Ipilimumab · CAT Metelimumab · Immunoglobulin E Omalizumab · Integrin Natalizumab · Interleukin 5 Mepolizumab · Interleukin-6 receptor Tocilizumab · TNFs Infliximab, Adalimumab, Certolizumab pegol, Afelimomab, Golimumab · LFA-1 Odulimomab other monoclonal: Atlizumab, Atorolimumab, Bertilimumab, Cedelizumab, Clenoliximab, Dorlimomab aritox, Dorlixizumab, Elsilimomab, Erlizumab, Faralimomab, Fontolizumab, Galiximab, Gantenerumab, Gomiliximab, Ibalizumab, Lebrilizumab, Lerdelimumab, Maslimomab, Morolimumab, Nerelimomab, Otelixizumab, Pexelizumab, Reslizumab, Rovelizumab, Siplizumab, Talizumab, Telimomab aritox, Toralizumab, Ustekinumab, Vapaliximab, Vepalimomab, Zolimomab aritox Polyclonal: Anti-thymocyte globulin -cept Fusion protein Abatacept, Aflibercept, Alefacept, Belatacept, Rilonacept, TNF inhibitor Etanercept IL-1 receptor antagonists Anakinra Intracellular Antimetabolites purine synthesis inhibitor: Azathioprine, Mycophenolic acid pyrimidine synthesis inhibitor: Leflunomide antifolate: Methotrexate Macrolides/ other IL-2 inhibitors diminished production, FKBP/Cyclophilin/Calcineurin: Tacrolimus, Ciclosporin, Pimecrolimus diminished response, mTOR: Sirolimus, Deforolimus, Everolimus, Temsirolimus, Zotarolimus other: Abetimus, Gusperimus TNF-a inhibitor Thalidomide Retrieved from http://en..org/wiki/Abatacept Categories: Monoclonal antibodies | Engineered proteinsHidden categories: Drug pages needing a structure drawing | All articles with statements | Articles with statements since August 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Polski This page was last modified on 8 August 2008, at 18:14
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