| 词条 | Givinostat |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 451563965 | IUPAC_name = {6-[(diethylamino)methyl]naphthalen-2-yl}methyl [4-(hydroxycarbamoyl)phenyl]carbamate | image = Givinostat structure.svg | alt = | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = — | legal_AU = | legal_CA = | legal_UK = | legal_US = IND | legal_status = | legal_EU_comment = Orphan status for sJIA | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | IUPHAR_ligand = 7490 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 497833-27-9 | ATCvet = | ATC_prefix = none | ATC_suffix = | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 5P60F84FBH | PubChem = 9804992 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID = 7980752 | smiles = O=C(OCc2cc1ccc(cc1cc2)CN(CC)CC)Nc3ccc(cc3)C(=O)NO | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | StdInChI = 1S/C24H27N3O4/c1-3-27(4-2)15-17-5-7-21-14-18(6-8-20(21)13-17)16-31-24(29)25-22-11-9-19(10-12-22)23(28)26-30/h5-14,30H,3-4,15-16H2,1-2H3,(H,25,29)(H,26,28) | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | StdInChIKey = YALNUENQHAQXEA-UHFFFAOYSA-N | C=24 | H=27 | N=3 | O=4 | molecular_weight = 421.489 g/mol }} Givinostat (INN[1]) or gavinostat (originally ITF2357) is a histone deacetylase inhibitor with potential anti-inflammatory, anti-angiogenic, and antineoplastic activities.[2] It is a hydroxamate used in the form of its hydrochloride. Givinostat is in numerous phase II clinical trials (including for relapsed leukemias and myelomas),[3] and has been granted orphan drug designation in the European Union for the treatment of systemic juvenile idiopathic arthritis,[4] polycythaemia vera.[5] and Duchenne muscular dystrophy. A preclinical study produced early results suggesting the molecule might help with diastolic dysfunction.[6] ITF2357 was discovered at Italfarmaco of Milan, Italy. It was patented in 1997 and first described in the scientific literature in 2005.[7][8] Adverse effectsIn clinical trials of givinostat as a salvage therapy for advanced Hodgkin's lymphoma, the most common adverse reactions were fatigue (seen in 50% of participants), mild diarrhea or abdominal pain (40% of participants), moderate thrombocytopenia (decreased platelet counts, seen in one third of patients), and mild leukopenia (a decrease in white blood cell levels, seen in 30% of patients). One-fifth of patients experienced prolongation of the QT interval, a measure of electrical conduction in the heart, severe enough to warrant temporary suspension of treatment.[9] Mechanism of actionGivinostat inhibits class I and class II histone deacetylases (HDACs) and several pro-inflammatory cytokines. This reduces expression of tumour necrosis factor (TNF), interleukin 1α and β, and interleukin 6.[8] It also has activity against cells expressing JAK2(V617F), a mutated form of the janus kinase 2 (JAK2) enzyme that is implicated in the pathophysiology of many myeloproliferative diseases, including polycythaemia vera.[10][11] In patients with polycythaemia, the reduction of mutant JAK2 concentrations by givinostat is believed to slow down the abnormal growth of erythrocytes and ameliorate the symptoms of the disease.[5] References1. ^{{cite journal | year = 2010 | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 63 | url = http://www.who.int/medicines/publications/druginformation/innlists/RL63.pdf | format = PDF | journal = WHO Drug Information | volume = 24 | issue = 1| pages = 58–9 }} 2. ^National Cancer Institute (2010). "Gavinostat". NCI Cancer Dictionary. U.S. National Institutes of Health. Retrieved 2010-09-15. 3. ^{{cite web|url=http://clinicaltrials.gov/ct2/results?term=ITF2357|publisher=ClinicalTrials.gov|title=Search results for ITF2357}} 4. ^{{cite web|author=Committee for Orphan Medicinal Products|date=23 February 2010|url=http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2010/02/WC500074739.pdf|title=Public summary of opinion on orphan designation: Givinostat for the treatment of systemic-onset juvenile idiopathic arthritis|publisher=European Medicines Agency|accessdate=2010-09-15}} 5. ^1 {{cite web|author=Committee for Orphan Medicinal Products|date=3 March 2010|url=http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2010/03/WC500075167.pdf|title=Public summary of opinion on orphan designation: Givinostat for the treatment of polycythaemia vera|publisher=European Medicines Agency}} 6. ^{{Cite news|url=https://www.sciencedaily.com/releases/2018/02/180207164033.htm|title=Potential treatment for diastolic dysfunction in heart failure|work=ScienceDaily|access-date=2018-08-19|language=en}} 7. ^WO patent application 1997/043251, "Compounds with anti-inflammatory and immunosuppressive activities", published 1997-11-20, assigned to Italfarmaco S.p.A. 8. ^1 {{cite journal | last1 = Leoni | first1 = F | last2 = Fossati | first2 = G | year = 2005 | title = The histone deacetylase inhibitor ITF2357 reduces production of pro-inflammatory cytokines in vitro and systemic inflammation in vivo | journal = Molecular Medicine | volume = 11 | issue = | page = 1 | doi = 10.2119/2006-00005.Dinarello | pmid = 16557334 | pmc=1449516}} 9. ^{{cite journal | last1 = Tan | first1 = J | last2 = Cang | first2 = S | last3 = Ma | first3 = Y | last4 = Petrillo | first4 = RL | last5 = Liu | first5 = D | year = 2010 | title = Novel histone deacetylase inhibitors in clinical trials as anti-cancer agents | journal = Journal of Hematology & Oncology | volume = 3 | issue = | page = 5 | doi = 10.1186/1756-8722-3-5 | pmid = 20132536 | pmc=2827364}} 10. ^{{cite journal | last1 = Vannucchi | first1 = AM | last2 = Guglielmelli | first2 = P | last3 = Pieri | first3 = L | last4 = Antonioli | first4 = E | last5 = Bosi | first5 = A | year = 2009 | title = Treatment options for essential thrombocythemia and polycythemia vera | url = http://www.medscape.com/viewarticle/589735 | journal = Expert Review of Hematology | volume = 2 | issue = 1| pages = 41–55 | doi = 10.1586/17474086.2.1.41 }} 11. ^{{cite journal | last1 = Guerini | first1 = V | last2 = Barbui | first2 = V | last3 = Spinelli | first3 = O |display-authors=etal | year = | date=April 2008 |title=The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F) | url = | journal = Leukemia | volume = 22 | issue = 4| pages = 740–7 | doi = 10.1038/sj.leu.2405049 | pmid = 18079739}} Further reading
4 : Hydroxamic acids|Histone deacetylase inhibitors|Orphan drugs|Experimental drugs |
| 随便看 |
|
开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。