| 词条 | Etravirine |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 443748530 | IUPAC_name = 4-[6-Amino-5-bromo-2-[(4-cyanophenyl)amino] pyrimidin-4-yl]oxy-3,5-dimethylbenzonitrile | image = Etravirine structure.svg | width = 150 | image2 = Etravirine ball-and-stick model.png | width2 = 185 | tradename = Intelence | Drugs.com = {{drugs.com|monograph|etravirine}} | MedlinePlus = a608016 | licence_EU = yes | licence_US = Etravirine | pregnancy_AU = B1 | pregnancy_US = B | legal_AU = S4 | legal_CA = Schedule VI | legal_UK = POM | legal_US = Rx-only | legal_status = | routes_of_administration = Oral | bioavailability = | protein_bound = 99.9% | metabolism = Hepatic (CYP3A4, CYP2C9 & CYP2C19-mediated) | elimination_half-life = 41±20 hours | excretion = Faeces (93.7%), urine (1.2%) | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 269055-15-4 | ATC_prefix = J05 | ATC_suffix = AG04 | PubChem = 193962 | DrugBank_Ref = {{drugbankcite|changed|drugbank}} | DrugBank = DB06414 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 168313 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 0C50HW4FO1 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D04112 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 308954 | NIAID_ChemDB = 105156 | PDB_ligand = 65B | C=20 | H=15 | Br=1 | N=6 | O=1 | molecular_weight = 435.28 g/mol | smiles = N#Cc3cc(c(Oc1nc(nc(c1Br)N)Nc2ccc(C#N)cc2)c(c3)C)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C20H15BrN6O/c1-11-7-14(10-23)8-12(2)17(11)28-19-16(21)18(24)26-20(27-19)25-15-5-3-13(9-22)4-6-15/h3-8H,1-2H3,(H3,24,25,26,27) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = PYGWGZALEOIKDF-UHFFFAOYSA-N }}Etravirine (ETR,[1] brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine.[2] Etravirine is marketed by Tibotec, a subsidiary of Johnson & Johnson. In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008.[3] It was also approved for use in Canada on April 1, 2008.[4] Etravirine is licensed in the United States, Canada, Israel, Russia, Australia and the European Union,[5] and is under regulatory review in Switzerland.[6] Indications and dosageEtravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents. The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine.[7] ContraindicationEach 100 mg etravirine tablet contains 160 mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.[8] Mechanism of actionEtravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine.[9] This potency appears to be related to etravirine's flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations.[10] Other diarylpyrimidine-analogues are currently being used as anti-HIV agents, notably rilpivirine. Warnings and risksIn 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop."[11] RepositioningEtravine has been studied for use in a drug repositioning application. In a paper[12] published in the medical publication Movement Disorders, Etravirine was shown to affect an increase in frataxin production. Frataxin deficiency is a key component to Friedreich's ataxia, a genetically inherited disease that causes the progressive loss of coordination and muscle strength leading to motor incapacitation and the full-time use of a wheelchair. References1. ^{{cite web |publisher=Department of Health and Human Services |work=Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents |url=http://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/34/appendix-a--key-to-acronyms |archive-url=https://web.archive.org/web/20120831103819/http://www.aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/34/appendix-a--key-to-acronyms |dead-url=yes |archive-date=2012-08-31 |title=Appendix A: Key to Acronyms }} 2. ^{{cite journal |author=Stellbrink HJ |title=Antiviral drugs in the treatment of AIDS: what is in the pipeline? |journal=Eur. J. Med. Res. |volume=12 |issue=9 |pages=483–95 |date=October 2007 |pmid=17933730 }} 3. ^{{cite web |url=http://ap.google.com/article/ALeqM5iCFQR1SKu681KqBBwrXJg1B6q5PAD8U8MS3G0 |title=FDA Approves HIV Drug Etravirine |publisher=Associated Press |date=January 18, 2008 }}{{dead link|date=November 2012|bot=Legobot}} 4. ^{{cite press release |title=First New NNRTI in Nearly a Decade to Benefit Canadians with HIV/AIDS |publisher=Janssen-Ortho Inc. |date=2008-04-01 |url=http://www.janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf |accessdate=2008-07-09 |format=PDF |deadurl=yes |archiveurl=https://web.archive.org/web/20101102080713/http://janssen-ortho.com/JOI/pdf_files/INTELENCE_Press_Release_E.pdf |archivedate=2010-11-02 |df= }} 5. ^{{cite web |url=http://www.tibotec.com/news/detail.jhtml?itemname=news_48 |publisher=Tibotec |title=Intelence receives marketing authorisation in the European Union for HIV combination therapy |accessdate=2008-08-29 |deadurl=yes |archiveurl=https://web.archive.org/web/20110928020018/http://www.tibotec.com/news/detail.jhtml?itemname=news_48 |archivedate=2011-09-28 |df= }} 6. ^{{cite web |url=http://www.aidsmap.com/en/news/46E8FC38-3BB8-4DDD-9FEC-D6BFD5DD69AA.asp |publisher=aidsmap |title=Etravirine (TMC125, Intelence) granted accelerated approval in US |accessdate=2008-01-24 }} 7. ^{{cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022187s008lbl.pdf |title=Intelence prescribing information |accessdate=January 19, 2012 |format=pdf |work=FDA}} 8. ^{{cite web |title=Etravine: Summary of product characteristics |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000900/WC500034180.pdf |page=5 |publisher=EMEA |accessdate=July 13, 2011}} 9. ^{{cite web |url=http://www.aidsmeds.com/articles/etravirine_tmc125_hiv_2042_13846.shtml |title=Etravirine—Countdown to Launch |accessdate=2008-02-02 |author=Evans, David |authorlink= |coauthors= |date=2008-01-15 |work= |publisher=AIDSmeds.com |pages= |language= |quote=}} 10. ^{{cite journal | vauthors = Das K, Clark AD, Lewi PJ, Heeres J, De Jonge MR, Koymans LM, Vinkers HM, Daeyaert F, Ludovici DW, Kukla MJ, De Corte B, Kavash RW, Ho CY, Ye H, Lichtenstein MA, Andries K, Pauwels R, De Béthune MP, Boyer PL, Clark P, Hughes SH, Janssen PA, Arnold E | title = Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants | journal = J. Med. Chem. | volume = 47 | issue = 10 | pages = 2550–60 | date = May 2004 | pmid = 15115397 | doi = 10.1021/jm030558s }} 11. ^{{cite web |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm180579.htm |title=FDA Medwatch Safety Information |accessdate=2009-08-27 |work=}} 12. ^{{cite web|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27604 | title=Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia |accessdate=2019-02-20 |work=}} External links
6 : Hepatotoxins|Non-nucleoside reverse transcriptase inhibitors|Pyrimidines|Nitriles|Organobromides|Belgian inventions |
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