| 词条 | Venetoclax |
| 释义 |
| drug_name = | IUPAC_name = 4-(4[2-(4-Chlorophenyl)-4,4-dimethyl-1-cyclohexen-1-yl]methyl1-piperazinyl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide | image = Venetoclax.svg | width = 275 | alt = | caption = | pronounce = Venclexta {{IPAc-en|v|ɛ|n|ˈ|k|l|ɛ|k|s|t|ə}} {{respell|ven|KLEKS|tə}} | tradename = Venclexta (US), Venclyxto (EU) | Drugs.com = {{Drugs.com|parent|venclexta}} | MedlinePlus = | pregnancy_AU = | pregnancy_AU_comment = | pregnancy_US = | pregnancy_category= | licence_EU = yes | legal_AU = | legal_AU_comment = | legal_CA = | legal_DE = | legal_NZ = | legal_UK = | legal_US = Rx-only | legal_UN = | legal_status = | routes_of_administration = Oral (tablets) | bioavailability = | protein_bound = >99.9%[1] | metabolism = Liver (CYP3A4, CYP3A5) | metabolites = | onset = | elimination_half-life = ~26 hours | duration_of_action = | excretion = Feces (>99.9%; 20.8% as unchanged venetoclax) | CAS_number = 1257044-40-8 | ATCvet = | ATC_prefix = L01 | ATC_suffix = XX52 | PubChem = 49846579 | ChemSpiderID = 29315017 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 133021 | DrugBank = DB11581 | UNII = N54AIC43PW | KEGG = D10679 | synonyms = GDC-0199, ABT-199, RG7601[2] | chemical_formula = | C=45 | H=50 | Cl=1 | N=7 | O=7 | S=1 | molecular_weight = 868.44 g/mol | SMILES = CC1(CCC(=C(C1)c2ccc(cc2)Cl)CN3CCN(CC3)c4ccc(c(c4)Oc5cc6cc[nH]c6nc5)C(=O)NS(=O)(=O)c7ccc(c(c7)[N+](=O)[O-])NCC8CCOCC8)C | StdInChI=1S/C45H50ClN7O7S/c1-45(2)15-11-33(39(26-45)31-3-5-34(46)6-4-31)29-51-17-19-52(20-18-51)35-7-9-38(42(24-35)60-36-23-32-12-16-47-43(32)49-28-36)44(54)50-61(57,58)37-8-10-40(41(25-37)53(55)56)48-27-30-13-21-59-22-14-30/h3-10,12,16,23-25,28,30,48H,11,13-15,17-22,26-27,29H2,1-2H3,(H,47,49)(H,50,54) COPY | StdInChIKey = LQBVNQSMGBZMKD-UHFFFAOYSA-N }}Venetoclax, sold under the trade name Venclexta and Venclyxto, is a medication used to treat chronic lymphocytic leukemia (CLL) in those who have failed first line treatment.[3] Medical usesVenetoclax is used as a second line treatment for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), who have shown disease progression after, or intolerance to a prior line of treatment.[3] Side effectsCommon side effects of venetoclax include neutropenia (low white blood cell count), nausea, anemia, diarrhea, upper respiratory tract infection, fatigue, and thrombocytopenia (low platelet count). Major side effects include tumor lysis syndrome and severe neutropenia. Additionally, this drug may cause fertility problems in males.[1] PharmacologyMechanism of actionVenetoclax blocks the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death of CLL cells. Overexpression of Bcl-2 in some lymphoid malignancies has sometimes shown to be linked with increased resistance to chemotherapy.[4] PharmacokineticsThe maximum plasma concentration achieved after oral administration occurred 5-8 hours after dose.[1] Steady state maximum concentration with low-fat meal conditions at the 400 mg once daily dose was found to be 2.1 ± 1.1 μg/mL. It is recommended that Venetoclax be administered with a meal.[1] The apparent volume of distribution for venetoclax is approximately 256–321 L. It is highly bound to human plasma protein. Within a concentration range of 1-30 μM (0.87-26 μg/mL), the fraction unbound in plasma was less than 0.01.[1] Venetoclax is metabolized by CYP3A4/5 as proven by in-vitro studies.[1] Those using the drug should not consume grapefruit products because they contain CYP3A inhibitors.[1] Additionally, while using venetoclax it is not recommended to use other drugs which contain CYP3A inhibitors (i.e.: erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, verapamil).[1] Venetoclax is excreted from the body via the fecal route.[1] HistoryIn 2015, the United States Food and Drug Administration (FDA) granted the breakthrough therapy designation to venetoclax for people with CLL or SLL who have relapsed, become intolerant to, or refractory to previous treatment. In 2016, the FDA approved venetoclax for use in those with CLL who have 17p deletion (deletion located on the chromosome 17 short arm) and who have been treated with at least one prior therapy.[1][5] Based on overall response rate, the indication was approved under accelerated FDA approval.[1] In October 2016 a European Medicines Agency committee recommended conditional marketing approval for venetoclax for CLL in the presence of 17p deletion or TP53 mutation; the drug had already been granted orphan status in 2012 for that use.[6] On June 8, 2018, the Food and Drug Administration granted regular approval to venetoclax for people with CLL or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least one prior therapy.[7] Society and cultureAbbVie Inc. of North Chicago Illinois manufactures Venclexta.[8] It is marketed by both Abbvie and Genentech USA, which is a member of the Roche Group.[8] AbbVie and Genentech are both commercializing the drug within the United States, but only AbbVie has rights to do so outside of the U.S.[9]According to Reuters 2016 Drugs to Watch, the 2020 forecast sales for Venetoclax are 1.48 billion.[10] Competition is expected from other drugs such as ibrutinib and idelalisib, both of which were also approved in 2014 to treat CLL.[10][11] Venclexta is patented by AbbVie Inc.[12]{{third-party-inline|date=November 2016}} ResearchAs of 2016 venetoclax had been tested to treat other hematological cancers, including non-Hodgkin’s lymphoma, multiple myeloma, diffuse large B-cell lymphoma and follicular lymphoma.[13] References1. ^1 2 3 4 5 6 7 8 9 10 {{cite web|title=US Venetoclax label|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208573s000lbl.pdf|publisher=FDA|date=April 2016}} 2. ^{{cite web|title=Venetoclax|url=http://adisinsight.springer.com/drugs/800034622|publisher=AdisInsight|accessdate=21 November 2016}} 3. ^1 {{cite web|title=FDA approves venetoclax for CLL or SLL, with or without 17p deletion, after one prior therapy|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm|publisher=U.S. Food and Drug Administration|language=en}}https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm610308.htm 4. ^{{Cite web|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208573Orig1s000SumR.pdf|title=Center for Drug Evaluation and Research - Application 208573Orig1s000 - Division Director Summary Review|last=|first=|date=|website=|publisher=Food and Drug Administration (FDA)|access-date=21 Nov 2016}} 5. ^{{cite web|title=FDA Approves New Drug for Chronic Lymphocytic Leukemia in Patients with a Specific Chromosomal Abnormality|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm|publisher=U.S. Food and Drug Administration|accessdate=14 April 2016|language=en}} 6. ^{{cite web|title=CHMP summary of positive opinion for Venclyxto|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004106/smops/Positive/human_smop_001041.jsp&mid=WC0b01ac058001d127&source=homeMedSearch&category=human|publisher=European Medicines Agency|accessdate=21 November 2016}} 7. ^{{cite web|title=FDA approves venetoclax for CLL or SLL, with or without 17p deletion, after one prior therapy|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm|publisher=U.S. Food and Drug Administration|language=en}}https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm610308.htm 8. ^1 {{Cite web|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm495253.htm|title=Press Announcements - FDA approves new drug for chronic lymphocytic leukemia in patients with a specific chromosomal abnormality|website=www.fda.gov|language=en|access-date=2016-11-16}} 9. ^{{Cite news|url=http://www.biopharmadive.com/news/inside-the-development-of-venclexta-abbvies-new-leukemia-drug/417965/|title=Inside the development of Venclexta, AbbVie's new leukemia drug|newspaper=BioPharma Dive|access-date=2016-11-16}} 10. ^1 {{Cite news|url=http://images.info.science.thomsonreuters.biz/Web/ThomsonReutersScience/%7B7e677448-1313-40ae-9978-6be1a8532a08%7D_A4_MarketInsight_Report_0213_012__edits_2.pdf|title=Drugs to Watch 2016 - Thomas Reuters|last=|first=|date=|work=|access-date=16 Nov 2016|via=}} 11. ^{{Cite news|url=http://www.onclive.com/web-exclusives/ibrutinib-and-idelalisib-continue-to-impress-in-cll-may-eventually-replace-chemotherapy-for-some-patients|title=Ibrutinib and Idelalisib Continue to Impress in CLL, May Eventually Replace Chemotherapy for Some Patients|newspaper=OncLive|access-date=2016-11-17}} 12. ^{{Cite web|url=http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=9,174,982&OS=9,174,982&RS=9,174,982|title=United States Patent: 9174982|website=patft.uspto.gov|access-date=2016-11-21}} 13. ^{{Cite web|url=http://images.info.science.thomsonreuters.biz/Web/ThomsonReutersScience/%7B7e677448-1313-40ae-9978-6be1a8532a08%7D_A4_MarketInsight_Report_0213_012__edits_2.pdf|title=Drugs to Watch 2016 - Market Insight Report|last=|first=|date=|website=|publisher=Thomson Reuters|access-date=16 Nov 2016}} 10 : Tetrahydropyrans|Sulfonamides|Benzamides|Pyrrolopyridines|Piperazines|Chloroarenes|Experimental cancer drugs|Breakthrough therapy|Cyclohexenes|Genentech |
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