| 词条 | Lebrikizumab |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 458270514 | image = | type = mab | mab_type = mab | source = zu | target = IL-13 | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = Investigational | routes_of_administration = Subcutaneous injection | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = none | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 953400-68-5 | ATC_prefix = none | ATC_suffix = | PubChemSubstance = 124490373 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = U9JLP7V031 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D09633 | synonyms = MILR1444A, RG3637 (formerly TNX-650) | C=6434 | H=9972 | N=1700 | O=2034 | S=50 | molecular_weight = }}Lebrikizumab (INN) is a humanized monoclonal antibody and an experimental immunosuppressive drug for the treatment of asthma that cannot be adequately controlled with inhalable glucocorticoids. The drug was created by Tanox under the name TNX-650, and a phase I clinical trial for refractory Hodgkin’s lymphoma had been performed when Genentech acquired Tanox in 2007.[1][2][3] It has successfully completed a Phase II clinical trial for the treatment of asthma.[4][5] Mechanism of actionLebrikizumab blocks interleukin 13 (IL-13), a cytokine (cell-signalling protein) that is produced by a type of white blood cell called Th2 cells. IL-13 is thought to induce the expression of another signalling protein, periostin, by epithelial cells of the bronchi. Periostin in turn seems to partake in a number of asthma related problems, such as bronchial hyperresponsiveness, inflammation, and activation and proliferation of airway fibroblasts, which are involved in airway remodelling.[5][6] This theory is supported by the fact that patients with high periostin levels responded significantly better to lebrikizumab in the Phase II study: the forced expiratory volume in 1 second (FEV1) was 8.2% higher than under placebo in this group (measured from the respective baselines), while low-periostin patients had 1.6% higher FEV1, and the average value for all patients was 5.5%. The FEV1 increase in low-periostin patients was not statistically significant.[7] Side effectsIn the study, musculoskeletal side effects were more common under lebrikizumab than under placebo (13.2% versus 5.4%). Other side effects were comparable in both groups: infections overall 48.1% versus 49.1%, upper airway infections 12.3% versus 14.3%, and severe side effects overall 3.8% (treatment) versus 5.3% (placebo).[7] References1. ^{{cite web |url=http://www.biospace.com/news_story.aspx?NewsEntityId=19463 |title=First Patient Dosed In Phase 1 Trial Of Tanox, Inc.'s TNX-650 - News, Search Jobs, Events |accessdate=8 July 2008 |format= |work=}} {{Monoclonals for immune system}}{{Immunosuppressants}}{{Interleukin receptor modulators}}2. ^{{cite web|url=http://www.cancer.gov/drugdictionary/?CdrID=539362|title=anti-IL-13 humanized monoclonal antibody TNX-650|work=NCI Drug Dictionary|publisher=National Cancer Institute|accessdate=10 December 2009}} 3. ^{{ClinicalTrialsGov|NCT00441818|Safety and Efficacy Study of TNX-650 to Treat Refractory Hodgkin's Lymphoma}} 4. ^{{ClinicalTrialsGov|NCT00930163|A Study of Lebrikizumab (MILR1444A) in Adult Patients With Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY)}} 5. ^1 {{Cite journal | last1 = Kraft | first1 = M. | title = Asthma Phenotypes and Interleukin-13 — Moving Closer to Personalized Medicine | doi = 10.1056/NEJMe1108666 | journal = New England Journal of Medicine | volume = 365 | issue = 12 | pages = 1141–1144 | year = 2011 | pmid = 21879891 | pmc = 4390041}} 6. ^{{cite web |url=http://www.prous.com/molecules/default.asp?ID=214 |title=Prous Science Molecule of the Month: Lebrikizumab |date=October 2011 |publisher=Thomson Reuters}} 7. ^1 {{Cite journal | last1 = Corren | first1 = J. | last2 = Lemanske | first2 = R. F. | last3 = Hanania | first3 = N. A. | last4 = Korenblat | first4 = P. E. | last5 = Parsey | first5 = M. V. | last6 = Arron | first6 = J. R. | last7 = Harris | first7 = J. M. | last8 = Scheerens | first8 = H. | last9 = Wu | first9 = L. C. | last10 = Su | doi = 10.1056/NEJMoa1106469 | first10 = Z. | last11 = Mosesova | first11 = S. | last12 = Eisner | first12 = M. D. | last13 = Bohen | first13 = S. P. | last14 = Matthews | first14 = J. G. | title = Lebrikizumab Treatment in Adults with Asthma | journal = New England Journal of Medicine | volume = 365 | issue = 12 | pages = 1088–1098 | year = 2011 | pmid = 21812663 | pmc = }} 1 : Monoclonal antibodies |
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