| 词条 | Daunorubicin |
| 释义 |
| Watchedfields = changed | verifiedrevid = 458300140 | drug_name = | IUPAC_name = (8S,10S)-8-Acetyl-10-[(2S,4S,5S,6S)- 4-amino-5-hydroxy-6-methyl-oxan- 2-yl]oxy-6,8,11-trihydroxy-1-methoxy- 9,10-dihydro-7H-tetracene-5,12-dione | image = Daunorubicin2DACS.svg | width = | image2 = Daunorubicin ball-and-stick.png | tradename = Cerubidine, others | Drugs.com = {{drugs.com|monograph|daunorubicin-hydrochloride}} | MedlinePlus = a682289 | pregnancy_category = D (U.S.) | legal_US = Rx-only | routes_of_administration = Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously | bioavailability = | protein_bound = | metabolism = Liver | elimination_half-life = 26.7 hours (metabolite) | excretion = Biliary and urinary | IUPHAR_ligand = 7063 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 20830-81-3 | ATC_prefix = L01 | ATC_suffix = DB02 | PubChem = 30323 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00694 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 28163 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = ZS7284E0ZP | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = C01907 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 41977 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 178 | C=27 | H=29 | N=1 | O=10 | molecular_weight = 527.52 g/mol 563.99 g/mol (HCl salt) | SMILES = C[C@H]1[C@H]([C@H](C[C@@H](O1)O[C@H]2C[C@@](Cc3c2c(c4c(c3O)C(=O)c5cccc(c5C4=O)OC)O)(C(=O)C)O)N)O | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C27H29NO10/c1-10-22(30)14(28)7-17(37-10)38-16-9-27(35,11(2)29)8-13-19(16)26(34)21-20(24(13)32)23(31)12-5-4-6-15(36-3)18(12)25(21)33/h4-6,10,14,16-17,22,30,32,34-35H,7-9,28H2,1-3H3/t10-,14-,16-,17-,22+,27-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = STQGQHZAVUOBTE-VGBVRHCVSA-N }}Daunorubicin, also known as daunomycin, is a chemotherapy medication used to treat cancer.[1] Specifically it is used for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and Kaposi's sarcoma.[1] It is used by injection into a vein.[1] A liposomal formulation known as liposomal daunorubicin also exists.[1] Common side effects include hair loss, vomiting, bone marrow suppression, and inflammation of the inside of the mouth.[1] Other severe side effects include heart disease and tissue death at the site of injection.[1] Use in pregnancy may harm the baby.[1] Daunorubicin is in the anthracycline family of medication.[2] It works in part by blocking the function of topoisomerase II.[1] Daunorubicin was approved for medical use in the United States in 1979.[1] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[3] The wholesale cost in the developing world is about 5.79 to 37.18 USD for a 20 mg vial.[4] This amount in the United Kingdom costs the NHS about 55.00 pounds.[2] It was originally isolated from bacteria of the Streptomyces type.[5] Medical usesIt slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as cytarabine), and its administration depends on the type of tumor and the degree of response. In addition to its major use in treating AML, daunorubicin is also used to treat neuroblastoma. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of chronic myelogenous leukemia. Daunorubicin is also used as the starting material for semi-synthetic manufacturing of doxorubicin, epirubicin and idarubicin. Mechanism of actionSimilar to doxorubicin, daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis.[6][7] This inhibits the progression of the enzyme topoisomerase II, which relaxes supercoils in DNA for transcription. Daunorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. On binding to DNA, daunomycin intercalates, with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C base pairs flanked on the 5' side by an A/T base pair. Crystallography shows that daunomycin induces a local unwinding angle of 8°, and other conformational disturbances of adjacent and second-neighbour base pairs.[8] It can also induce histone eviction from chromatin upon intercalation.[9][10] History{{See also|Anthracycline#History|Doxorubicin#History|History of cancer chemotherapy}}In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle in Apulia. A new strain of Streptomyces peucetius which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against murine tumors. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name Dauni, a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, rubis, describing the color.[11][12][13] Clinical trials began in the 1960s, and the drug saw success in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could produce fatal cardiac toxicity.[14] In 2015-16, a team at Ohio State University "showed that, by carefully manipulating strands of viral DNA, an origami structure with complex folds can be created in just 10 minutes. Incredibly, these structures are only 100 nanometers across – that’s 1,000 times smaller than the width of a human hair. Small volumes of daunorubicin can be wrapped up in these minuscule pods, which can then be released into a leukemia cell-filled environment."[15]{{medrs|date=August 2018}} Route of administrationDaunorubicin should only be administered in a rapid intravenous infusion. It should not be administered intramuscularly or subcutaneously, since it may cause extensive tissue necrosis. It should also never be administered intrathecally (into the spinal canal), as this will cause extensive damage to the nervous system and may lead to death. Daunorubicin has been used intravitreally (inside the eye) for the purposes of preventing proliferative vitreoretinopathy, a common complication following retinal detachment surgery, but has not been found to be effective and is not used for any other ophthalmic purposes at this time.[16] See also
References1. ^1 2 3 4 5 6 7 8 {{cite web|title=daunorubicin hydrochloride|url=https://www.drugs.com/monograph/daunorubicin-hydrochloride.html|publisher=The American Society of Health-System Pharmacists|accessdate=8 December 2016|deadurl=no|archiveurl=https://web.archive.org/web/20170108211655/https://www.drugs.com/monograph/daunorubicin-hydrochloride.html|archivedate=8 January 2017|df=}} 2. ^1 {{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=581–583|edition=69}} 3. ^{{cite web|title=WHO Model List of Essential Medicines (19th List)|url=http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|work=World Health Organization|accessdate=8 December 2016|date=April 2015|deadurl=no|archiveurl=https://web.archive.org/web/20161213052708/http://www.who.int/medicines/publications/essentialmedicines/EML_2015_FINAL_amended_NOV2015.pdf?ua=1|archivedate=13 December 2016|df=}} 4. ^{{cite web|title=Daunorubicin|url=http://mshpriceguide.org/en/single-drug-information/?DMFId=1298&searchYear=2014|website=International Drug Price Indicator Guide|accessdate=8 December 2016}} 5. ^{{cite book|last1=Lin|first1=Guo-Qiang|last2=You|first2=Qi-Dong|last3=Cheng|first3=Jie-Fei|title=Chiral Drugs: Chemistry and Biological Action|date=2011|publisher=John Wiley & Sons|isbn=9781118075630|page=120|url=https://books.google.ca/books?id=Zgx13oMZaYUC&pg=PA120|language=en|deadurl=no|archiveurl=https://web.archive.org/web/20161221092042/https://books.google.ca/books?id=Zgx13oMZaYUC&pg=PA120|archivedate=2016-12-21|df=}} 6. ^{{cite journal |vauthors=Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA |title=Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells |journal=Mol Pharmacol |volume=45 |issue=4 |pages=649–56 |date=April 1994 |pmid=8183243}} 7. ^{{cite journal |vauthors=Momparler RL, Karon M, Siegel SE, Avila F |title=Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells |journal=Cancer Res |volume=36 |issue=8 |pages=2891–5 |date=August 1976 |pmid=1277199 |url=http://cancerres.aacrjournals.org/cgi/reprint/36/8/2891 |deadurl=no |archiveurl=https://web.archive.org/web/20090205063327/http://cancerres.aacrjournals.org/cgi/reprint/36/8/2891 |archivedate=2009-02-05 |df= }} 8. ^{{Cite journal |title = Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG) |author = G J Quigley |author2 = A H Wang |author3 = G Ughetto |author4 = G van der Marel |author5 = J H van Boom |author6 = A Rich |last-author-amp = yes |journal = PNAS |date = December 1980 |volume = 77 |issue = 12 |pages = 7204–7208 |url = http://www.pnas.org/content/77/12/7204.short |doi = 10.1073/pnas.77.12.7204 |deadurl = no |archiveurl = https://web.archive.org/web/20150924164649/http://www.pnas.org/content/77/12/7204.short |archivedate = 2015-09-24 |df = |pmc = 350470 }} 9. ^{{cite journal |vauthors= Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J |title= Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin |journal= Nature Communications |volume= 4 |pages= 1908 |year= 2013 |url= http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2921.html |pmid= 23715267 |doi= 10.1038/ncomms2921 |pmc= 3674280 |deadurl= no |archiveurl= https://web.archive.org/web/20150802005517/http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2921.html |archivedate= 2015-08-02 |df= }} 10. ^{{cite journal |vauthors= Pang B, de Jong J, Qiao X, Wessels LF, Neefjes J |title= Chemical profiling of the genome with anti-cancer drugs defines target specificities |journal= Nature Chemical Biology |volume=11 |pages=472–80 |year=2015 |url=http://www.nature.com/nchembio/journal/v11/n7/full/nchembio.1811.html |pmid= 25961671 |doi=10.1038/nchembio.1811 |issue=7}} 11. ^{{cite journal |author=Weiss RB |title=The anthracyclines: will we ever find a better doxorubicin? |journal=Seminars in Oncology |volume=19 |issue=6 |pages=670–86 |date=December 1992 |pmid=1462166}} 12. ^{{cite journal | pmid = 5332105 | volume=60 | title=Clinical trials in Plasmodium falciparum malaria with a long-acting sulphonamide | year=1966 | journal=Trans. R. Soc. Trop. Med. Hyg. | pages=222–4 | vauthors=Baruffa G | doi=10.1016/0035-9203(66)90030-7}} 13. ^Per prior citation, the first publication: Camerino B, Palamidessi G (1960) Derivati della parazina II. Sulfonamdopir (in Italian). Gazz Chim Ital 90:1802–1815 14. ^{{cite journal |vauthors=Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA |title=Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia |journal=Cancer |volume=20 |issue=3 |pages=333–53 |date=March 1967 |pmid=4290058 |doi=10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K}} 15. ^{{cite web | url = http://www.iflscience.com/health-and-medicine/researchers-kill-drug-resistant-leukemia-cells-using-dna-trojan-horse-attack | title = http://www.iflscience.com/health-and-medicine/researchers-kill-drug-resistant-leukemia-cells-using-dna-trojan-horse-attack/ | publisher = IFL Science }} 16. ^{{cite journal | author= Mortensen, ME | title= Inadvertent intrathecal injection of daunorubicin with fatal outcome | journal=Med Pediatr Oncol| year= 1992 | volume= 20 | issue= 3 | pages= 249–253 | pmid= 1574039|display-authors=etal | doi=10.1002/mpo.2950200315}} External links
7 : Anthracyclines|Anthraquinone glycosides|Topoisomerase inhibitors|IARC Group 2B carcinogens|World Health Organization essential medicines|RTT|DNA intercalaters |
| 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。