| 词条 | Idelalisib | |||||||||||||||
| 释义 |
| IUPAC_name = 5-Fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]-4(3H)-quinazolinone | image = Idelalisib.svg | width = 175 | alt = | caption = Idelalisib structure | tradename = Zydelig | pronounce = {{IPAc-en|aɪ|ˈ|d|ɛ|l|ə|l|ɪ|s|ɪ|b}} {{respell|eye|DEL|ə|li|sib}} | Drugs.com = {{Drugs.com|parent|zydelig}} | MedlinePlus = | pregnancy_AU = | pregnancy_US = D | pregnancy_category = | licence_EU = yes | legal_AU = | legal_CA = | legal_UK = | legal_US = Rx-only | legal_status = ℞-only | routes_of_administration = Oral (tablets) | bioavailability = | protein_bound = >84%[1] | metabolism = Aldehyde oxidase (~70%), CYP3A4 (~30%);[2] UGT1A4 (minor) | metabolites = GS-563117 (inactive in vitro) | onset = Tmax = 1.5 hours | elimination_half-life = 8.2 hours | excretion = Feces (78%), urine (14%) | CAS_number = 870281-82-6 | ATCvet = | ATC_prefix = L01 | ATC_suffix = XX47 | PubChem = 11625818 | DrugBank = DB09054 | ChemSpiderID = 9800565 | ChEMBL = 2216870 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 82701 | KEGG = D10560 | synonyms = GS-1101, CAL-101 | C=22 | H=18 | F=1 | N=7 | O=1 | molecular_weight = 415.42 g/mol | smiles = CC[C@H](Nc1ncnc2nc[nH]c12)c4nc3cccc(F)c3c(=O)n4c5ccccc5 | StdInChI=1S/C22H18FN7O/c1-2-15(28-20-18-19(25-11-24-18)26-12-27-20)21-29-16-10-6-9-14(23)17(16)22(31)30(21)13-7-4-3-5-8-13/h3-12,15H,2H2,1H3,(H2,24,25,26,27,28)/t15-/m0/s1 | StdInChIKey = IFSDAJWBUCMOAH-HNNXBMFYSA-N }} Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers. The substance acts as a phosphoinositide 3-kinase inhibitor; more specifically, it blocks P110δ, the delta isoform of the enzyme phosphoinositide 3-kinase.[4] It was developed by Gilead Sciences. Idelalisib had annual sales of $168 million (USD) during the year of 2016, up from $132 million (USD) in 2015.[3] Medical usesIdelalisib is a second-line drug for patients whose chronic lymphocytic leukemia (CLL) has relapsed. Used in combination with rituximab,[6] idelalisib is to be used in patients for whom rituximab alone would be considered appropriate therapy due to other existing medical conditions.[6] It appears to be effective and leads improvement of lymphadenopathy and splenomegaly. However, the lymphocyte counts take longer to decrease to normal levels with idelalisib. It is also approved for the treatment of follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL), both in patients who have received at least two prior systemic therapies.[1] Adverse effectsClinical symptoms include diarrhea, fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash. Laboratory abnormalities may include: neutropenia, hypertriglyceridemia, hyperglycemia and elevated levels of liver enzymes. Idelalisib's safety and effectiveness to treat relapsed FL and relapsed SLL were established in a clinical trial with 123 participants with slow-growing (indolent) non-Hodgkin lymphomas. All participants were treated with idelalisib and were evaluated for complete or partial disappearance of their cancer after treatment (objective response rate, or ORR). Results showed 54% of participants with relapsed FL and 58% of participants with SLL experienced ORR.[9] The U.S. label for idelalisib has a boxed warning describing toxicities that can be serious and fatal, including liver toxicity, severe diarrhea, colon inflammation, lung tissue inflammation (pneumonitis) and intestinal perforation, and the manufacturer was required to put in place a Risk Evaluation and Mitigation Strategy (REMS) under which the risk of toxicities would be managed.[4] In March 2016, as reports were made from three ongoing clinical trials of serious adverse events and deaths, mostly due to infections, the European Medicines Agency opened a review of the drug and its risks.[5] On March 21, 2016 Gilead Sciences (the manufacturer of idelalisib) alerted healthcare providers about decreased overall survival and increased risk of serious infections in patients with CLL and indolent non-Hodgkin lymphoma (iNHL) treated with idelalisib.[6] The company also disclosed that it stopped six clinical trials in patients with CLL, SLL and iNHL due to an increased rate of adverse events, including deaths.[7] PharmacologyMechanism of actionPI3Kδ kinase is expressed in normal and malignant B-cells. By inhibiting it, idelalisib induces apoptosis and prevents proliferation in cell lines derived from malignant B-cells and in primary tumor cells. It also inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow.[1]Binding profileIdelalisib is a competitive inhibitor of the ATP binding site of the PI3Kδ catalytic domain. Its in vitro potency and selectivity relative to the other Class I PI3K isoforms is the following:[8]
HistoryRegulatoryIn July 2014, the FDA and EMA granted idelalisib approval to treat different types of leukemia.[9][17] The FDA is also granted approval for idelalisib to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma. Idelalisib is intended to be used in patients who have received at least two prior systemic therapies. References1. ^1 2 {{cite web|title=ZYDELIG (idelalisib) Tablets, for Oral Use. U.S. Full Prescribing Information|url=https://www.zydelig.com/include/media/pdf/full-prescribing-information.pdf|publisher=Gilead Sciences, Inc.|accessdate=15 April 2016}} [9][10][11][12]2. ^{{cite web|title=Clinical Pharmacology and Biopharmaceutics Review: Zydelig (idelalisib)|url=http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206545Orig1s000ClinPharmR.pdf|website=U.S. Food and Drug Administration|accessdate=15 April 2016|page=6}} 3. ^{{cite web |url= https://www.pharmacompass.com/sales-forecast/idelalisib|title= Annual Sales of Idelalisib reported using PharmaCompass' compilation of Annual Reports of Global Pharmaceutical Companies.|author= |publisher= Pharmacompass|access-date= January 21, 2019}} 4. ^{{Cite web|url=http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm|title=Press Announcements — FDA approves Zydelig for three types of blood cancers|website=www.fda.gov|language=en|access-date=2016-03-14}} 5. ^{{Cite web|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/03/news_detail_002487.jsp&mid=WC0b01ac058004d5c1|title=European Medicines Agency — News and Events — EMA reviews cancer medicine Zydelig|website=www.ema.europa.eu|access-date=2016-03-14}} 6. ^{{cite web|title=Important Drug Warning: Decreased Overall Survival and Increased Risk of Serious Infections in Patients Receiving ZYDELIG (idelalisib)|url=http://zydelig.com/Content/pdf/Zydelig-Safety-Info-FINAL.pdf|publisher=Gilead Sciences, Inc.|accessdate=19 April 2016|date=March 21, 2016}} 7. ^{{cite web|title=Drug Safety and Availability — FDA Alerts Healthcare Professionals About Clinical Trials with Zydelig (idelalisib) in Combination with Other Cancer Medicines|url=http://www.fda.gov/Drugs/DrugSafety/ucm490618.htm|publisher=FDA Center for Drug Evaluation and Research|accessdate=19 April 2016|language=en}} 8. ^{{cite web|title=Committee for Medicinal Products for Human Use Assessment Report: Zydelig (idelalisib)|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003843/WC500175379.pdf|publisher=European Medicines Agency|accessdate=19 April 2016|page=17}} 9. ^1 {{Cite journal | last1 = Wu | first1 = M. | last2 = Akinleye | first2 = A. | last3 = Zhu | first3 = X. | title = Novel agents for chronic lymphocytic leukemia | doi = 10.1186/1756-8722-6-36 | journal = Journal of Hematology & Oncology | volume = 6 | pages = 36 | year = 2013 | pmid = 23680477 | pmc =3659027 }} 10. ^1 2 {{cite journal | doi = 10.1056/NEJMoa1315226 | title = Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia | year = 2014 | last1 = Furman | first1 = Richard R. | last2 = Sharman | first2 = Jeff P. | last3 = Coutre | first3 = Steven E. | last4 = Cheson | first4 = Bruce D. | last5 = Pagel | first5 = John M. | last6 = Hillmen | first6 = Peter | last7 = Barrientos | first7 = Jacqueline C. | last8 = Zelenetz | first8 = Andrew D. | last9 = Kipps | first9 = Thomas J. | last10 = Flinn | first10 = Ian | last11 = Ghia | first11 = Paolo | last12 = Eradat | first12 = Herbert | last13 = Ervin | first13 = Thomas | last14 = Lamanna | first14 = Nicole | last15 = Coiffier | first15 = Bertrand | last16 = Pettitt | first16 = Andrew R. | last17 = Ma | first17 = Shuo | last18 = Stilgenbauer | first18 = Stephan | last19 = Cramer | first19 = Paula | last20 = Aiello | first20 = Maria | last21 = Johnson | first21 = Dave M. | last22 = Miller | first22 = Langdon L. | last23 = Li | first23 = Daniel | last24 = Jahn | first24 = Thomas M. | last25 = Dansey | first25 = Roger D. | last26 = Hallek | first26 = Michael | last27 = O'Brien | first27 = Susan M. | journal = New England Journal of Medicine | pages = 997–1007 | pmid=24450857 | volume=370 | pmc=4161365}} 11. ^1 2 {{cite web | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm | title = FDA approves Zydelig for three types of blood cancers | date = July 23, 2014 | publisher = Food and Drug Administration}} 12. ^1 {{cite web | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2014/07/news_detail_002148.jsp | date = July 25, 2014 | title = European Medicines Agency recommends approval of two new treatment options for rare cancers | publisher = European Medicines Agency}} }} External links
5 : Antineoplastic drugs|Breakthrough therapy|Phosphoinositide 3-kinase inhibitors|Purines|Fluoroarenes |
|||||||||||||||
| 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。