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Revision as of 14:26, 31 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit Latest revision as of 07:05, 23 August 2024 edit undoBoghog (talk | contribs)Autopatrolled, Extended confirmed users, IP block exemptions, New page reviewers, Pending changes reviewers, Rollbackers, Template editors137,518 edits consistent citation formatting 
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{{Short description|Chemotherapy medication}}
{{Use dmy dates|date=March 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox {{Drugbox
| Verifiedfields = changed | Watchedfields = changed
| verifiedrevid = 401978544 | verifiedrevid = 458300140
⚫ | image = Daunorubicin2DACS.svg
⚫ | IUPAC_name = (8''S'',10''S'')-8-acetyl-10-oxy-6,8,11-trihydroxy-1-methoxy-<br>9,10-dihydro-7''H''-tetracene-5,12-dione
| width =
⚫ | image = Daunorubicin.svg
| width = 200px | alt =
| image2 = Daunorubicin ball-and-stick.png
| alt2 =


<!--Clinical data--> <!-- Clinical data -->
| tradename = Cerubidine | tradename = Cerubidine, others
| Drugs.com = {{drugs.com|monograph|daunorubicin-hydrochloride}} | Drugs.com = {{drugs.com|monograph|daunorubicin-hydrochloride}}
| MedlinePlus = a682289 | MedlinePlus = a682289
| pregnancy_AU = D
| pregnancy_category = D (])
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Daunorubicin (Cerubidine) Use During Pregnancy | website=Drugs.com | date=19 September 2019 | url=https://www.drugs.com/pregnancy/daunorubicin.html | access-date=15 August 2020}}</ref>
| legal_status =
| routes_of_administration = Exclusively ]. Causes severe ] if administered ]ly or ]ly | routes_of_administration = ]
⚫ | ATC_prefix = L01
⚫ | ATC_suffix = DB02

| legal_AU = S4
| legal_US = Rx-only


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->
| bioavailability = | bioavailability =
| protein_bound = | protein_bound =
| metabolism = ] | metabolism = ]
| elimination_half-life = 26.7 ]s (metabolite) | elimination_half-life = 26.7 ]s (metabolite)
| excretion = Biliary and urinary | excretion = ] and urinary


<!--Identifiers--> <!-- Identifiers -->
| IUPHAR_ligand = 7063
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}} | CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 20830-81-3 | CAS_number = 20830-81-3
⚫ | ATC_prefix = L01
⚫ | ATC_suffix = DB02
| PubChem = 30323 | PubChem = 30323
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
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| UNII_Ref = {{fdacite|correct|FDA}} | UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ZS7284E0ZP | UNII = ZS7284E0ZP
| KEGG_Ref = {{keggcite|changed|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C01907 | KEGG = C01907
| ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 41977 | ChEBI = 41977
| ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 178 | ChEMBL = 178


<!--Chemical data--> <!-- Chemical data -->
⚫ | IUPAC_name = (8''S'',10''S'')-8-Acetyl-10-oxy-6,8,11-trihydroxy-1-methoxy-<br>9,10-dihydro-7''H''-tetracene-5,12-dione
| C=27 | H=29 | N=1 | O=10 | C=27 | H=29 | N=1 | O=10
⚫ | SMILES = C1((C(O1)O2C(Cc3c2c(c4c(c3O)C(=O)c5cccc(c5C4=O)OC)O)(C(=O)C)O)N)O
| molecular_weight = 527.52 ]/]<br>563.99 ]/] (] salt)
⚫ | smiles = C1((C(O1)O2C(Cc3c2c(c4c(c3O)C(=O)c5cccc(c5C4=O)OC)O)(C(=O)C)O)N)O
| InChI = 1/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
| InChIKey = STQGQHZAVUOBTE-VGBVRHCVBQ
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | 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 | 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
Line 52: Line 58:
| StdInChIKey = STQGQHZAVUOBTE-VGBVRHCVSA-N | StdInChIKey = STQGQHZAVUOBTE-VGBVRHCVSA-N
}} }}
<!-- Definition and medical uses -->
'''Daunorubicin''' or '''daunomycin''' (daunomycin cerubidine) is ] of the ] family that is given as a treatment for some types of ]. It is most commonly used to treat specific types of ] (] and ]). It was initially isolated from '']''.
'''Daunorubicin''', also known as '''daunomycin''', is a ] used to treat ].<ref name=AHFS2016/> Specifically it is used for ] (AML), ] (ALL), ] (CML), and ].<ref name=AHFS2016/> It is administered by ].<ref name=AHFS2016/> A ] formulation known as ] also exists.<ref name=AHFS2016/>


<!-- Side effects and mechanisms -->
A ] formulation of daunorubicin is marketed in the United States as '''DaunoXome'''.
Common side effects include hair loss, vomiting, ], and inflammation of the inside of the mouth.<ref name=AHFS2016/> Other severe side effects include ] and ] at the site of injection.<ref name=AHFS2016/> Use in ] may harm the fetus.<ref name=AHFS2016>{{cite web |title=Daunorubicin hydrochloride |url= https://www.drugs.com/monograph/daunorubicin-hydrochloride.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016|url-status=live|archive-url= https://web.archive.org/web/20170108211655/https://www.drugs.com/monograph/daunorubicin-hydrochloride.html |archive-date=8 January 2017 }}</ref> Daunorubicin is in the ] family of medication.<ref name=BNF69>{{cite book|title=British National Formulary: BNF 69 |date=2015 |publisher=British Medical Association |isbn=9780857111562 |pages=581–583 |edition=69th }}</ref> It works in part by blocking the function of ].<ref name=AHFS2016/>


<!-- History, society and culture -->
⚫ ==History==
Daunorubicin was approved for medical use in the United States in 1979.<ref name=AHFS2016/> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It was originally isolated from bacteria of the '']'' type.<ref>{{cite book| vauthors = Lin GQ, You QD, Cheng JF |title=Chiral Drugs: Chemistry and Biological Action|date=2011|publisher=John Wiley & Sons|isbn=9781118075630|page=120|url=https://books.google.com/books?id=Zgx13oMZaYUC&pg=PA120|language=en|url-status=live|archive-url=https://web.archive.org/web/20161221092042/https://books.google.ca/books?id=Zgx13oMZaYUC&pg=PA120|archive-date=21 December 2016}}</ref>
⚫ {{See also|Doxorubicin#History|History of cancer chemotherapy}}
⚫ In the 1950s, an ] research company, Farmitalia Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based ]s. A soil sample was isolated from the area surrounding the ], a 13th century castle in ]. A new strain of '']'' which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against ]s. Since a group of ] researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name '']'', a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ], ''rubis'', describing the color.<ref name="weiss">{{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 |year=1992 |month=December |pmid=1462166}}</ref> 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.<ref name="TanC">{{cite journal |author=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 |year=1967 |month=March |pmid=4290058 |doi=10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K}}</ref>


==Uses== ==Medical uses==
It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as ]), and its administration depends on the type of tumor and the degree of response. It slows or stops the growth of cancer cells in the body. Treatment is usually performed together with other chemotherapy drugs (such as ]), and its administration depends on the type of tumor and the degree of response.{{cn|date=May 2023}}


In addition to its major use in treating ], daunorubicin is also used to treat ]. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of ]. In addition to its major use in treating acute myeloid leukemia, daunorubicin is also used to treat ]. Daunorubicin has been used with other chemotherapy agents to treat the blastic phase of ].{{cn|date=June 2023}}


Daunorubicin is also used as the starting material for semi-synthetic manufacturing of ], ] and ]. Daunorubicin is also used as the starting material for semi-synthetic manufacturing of ], ] and ].{{cn|date=March 2024}}


==Mode of action== == Mechanism of action ==
Similar to ], daunorubicin interacts with DNA by ] and inhibition of macromolecular ].<ref name="fornari">{{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 = Molecular Pharmacology | volume = 45 | issue = 4 | pages = 649–656 | date = April 1994 | pmid = 8183243 }}</ref><ref name="momparler">{{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 Research | volume = 36 | issue = 8 | pages = 2891–2895 | date = August 1976 | pmid = 1277199 | url = http://cancerres.aacrjournals.org/cgi/reprint/36/8/2891 | url-status = live | archive-url = https://web.archive.org/web/20090205063327/http://cancerres.aacrjournals.org/cgi/reprint/36/8/2891 | archive-date = 5 February 2009 }}</ref> This inhibits the progression of the enzyme ], which relaxes supercoils in DNA; without action of topoisomerase II, these DNA supercoils interfere in ] of DNA. 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 ].
On binding to DNA, daunomycin ], with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C ]s flanked on the 5' side by an A/T base pair. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 11<sup>o</sup>, but negligible distortion of helical conformation. {{Citation needed|date=September 2011}}
On binding to DNA, daunomycin ], with its daunosamine residue directed toward the minor groove. It has the highest preference for two adjacent G/C ]s 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.<ref>{{cite journal | vauthors = Quigley GJ, Wang AH, Ughetto G, van der Marel G, van Boom JH, Rich A | title = Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 12 | pages = 7204–7208 | date = December 1980 | pmid = 6938965 | pmc = 350470 | doi = 10.1073/pnas.77.12.7204 | doi-access = free | bibcode = 1980PNAS...77.7204Q }}</ref>
It can also induce ] eviction from ] upon ].<ref name="Pang">{{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 | pmid = 23715267 | pmc = 3674280 | doi = 10.1038/ncomms2921 | bibcode = 2013NatCo...4.1908P }}</ref><ref name="pang">{{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 | issue = 7 | pages = 472–480 | date = July 2015 | pmid = 25961671 | doi = 10.1038/nchembio.1811 }}</ref>

⚫ == History ==
⚫ {{See also|Anthracycline#History|Doxorubicin#History|History of cancer chemotherapy}}
⚫ In the 1950s, an ] research company, ] Research Laboratories, began an organized effort to isolate anticancer compounds from soil-based ]s. A soil sample was isolated from the area surrounding the ], a 13th-century castle in ]. A new strain of '']'' which produced a red pigment was isolated, and an antibiotic was produced from this bacterium that was found to have good activity against ] tumors. Since a group of ] researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name '']'', a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ], ''rubis'', describing the color.<ref name="weiss">{{cite journal | vauthors = Weiss RB | title = The anthracyclines: will we ever find a better doxorubicin? | journal = Seminars in Oncology | volume = 19 | issue = 6 | pages = 670–686 | date = December 1992 | pmid = 1462166 }}</ref><ref>{{cite journal | vauthors = Baruffa G | title = Clinical trials in Plasmodium falciparum malaria with a long-acting sulphonamide | journal = Transactions of the Royal Society of Tropical Medicine and Hygiene | volume = 60 | issue = 2 | pages = 222–224 | year = 1966 | pmid = 5332105 | doi = 10.1016/0035-9203(66)90030-7 }}</ref><ref>{{cite journal | vauthors = Camerino B, Palamidessi G | date = 1960 | title = Derivati della parazina II. Sulfonamdopir | trans-title = Derivatives of parazine II. Sulfonamdopir | language = Italian | journal = Gazzetta Chimica Italiana | trans-journal = Italian Chemical Journal | volume = 90 | pages = 1802–1815 }}</ref> 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.<ref name="TanC">{{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 = 333–353 | date = March 1967 | pmid = 4290058 | doi = 10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K | s2cid = 19272219 | doi-access = free }}</ref>

In 2015–16, a team at ] "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."<ref>{{cite web | url = http://www.iflscience.com/health-and-medicine/researchers-kill-drug-resistant-leukemia-cells-using-dna-trojan-horse-attack | title = Researchers kill drug-resistant leukemia cells using DNA Trojan horse attack | date = 25 February 2016 | publisher = IFL Science }}</ref><ref>{{cite journal | vauthors = Halley PD, Lucas CR, McWilliams EM, Webber MJ, Patton RA, Kural C, Lucas DM, Byrd JC, Castro CE | title = Daunorubicin-Loaded DNA Origami Nanostructures Circumvent Drug-Resistance Mechanisms in a Leukemia Model | journal = Small | volume = 12 | issue = 3 | pages = 308–320 | date = January 2016 | pmid = 26583570 | pmc = 4879968 | doi = 10.1002/smll.201502118 }}</ref>{{medrs|date=August 2018}}


==Route of administration== ==Route of administration==
Daunorubicin should only be administered in a rapid ]. It should not be administered ]ly or ]ly, since it may cause extensive tissue ]. Daunorubicin should only be administered in a rapid ]. It should not be administered ]ly or ]ly, since it may cause extensive tissue ].
It should also '''never''' be administered ]ly (into the ]), as this will cause extensive damage to the ] and may lead to ].<ref> It should also never be administered ]ly (into the ]), as this will cause extensive damage to the ] and may lead to ]. 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.<ref>{{cite journal | vauthors = Mortensen ME, Cecalupo AJ, Lo WD, Egorin MJ, Batley R | title = Inadvertent intrathecal injection of daunorubicin with fatal outcome | journal = Medical and Pediatric Oncology | volume = 20 | issue = 3 | pages = 249–253 | year = 1992 | pmid = 1574039 | doi = 10.1002/mpo.2950200315 }}</ref>
{{cite journal | author= Mortensen, ME ''et al.'' | title= Inadvertent intrathecal injection of daunorubicin with fatal outcome | journal= | year= 1992 | volume= 20 | issue= 3 | pages= 249–253 | pmid= 1574039}}</ref>


==References== == References ==
{{reflist}} {{reflist}}

== External links ==
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{{Chemotherapeutic agents}} {{Chemotherapeutic agents}}
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