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Daunorubicin or daunomycin (daunomycin cerubidine) is chemotherapeutic of the anthracycline family that is given as a treatment for some types of cancer. It is most commonly used to treat specific types of leukaemia (acute myeloid leukemia and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.

A liposomal formulation of daunorubicin is marketed in the United States as DaunoXome.

History[edit]

See also: Doxorubicin#History and 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.^[1] 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.^[2]

Uses[edit]

It 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 action[edit]

Cartoon diagram of two doxorubicin molecules intercalating DNA, ^[3]

Similar to Doxorubicin, Daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis.^[4]^[5] 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. Daunomycin effectively binds to every 3 base pairs and induces a local unwinding angle of 11°, but negligible distortion of helical conformation.^[6] It can also induce histone eviction from chromatin upon intercalation.^[7]

Route of administration[edit]

Daunorubicin 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.^[8]

References[edit]

^ Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology 19 (6): 670–86. PMID 1462166.
^ Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA (March 1967). "Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia". Cancer 20 (3): 333–53. doi:10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K. PMID 4290058.
^ http://www.rcsb.org/pdb/explore.do?structureId=1D12
^ Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (April 1994). "Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells". Mol Pharmacol 45 (4): 649–56. PMID 8183243.
^ Momparler RL, Karon M, Siegel SE, Avila F (August 1976). "Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells". Cancer Res 36 (8): 2891–5. PMID 1277199.
^ G J Quigley, A H Wang, G Ughetto, G van der Marel, J H van Boom, and A Rich (December 1980). "Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG)". PNAS 77 (12): 7204–7208.
^ 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 (2013). "Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin". Nature Communications 4: 1908. doi:10.1038/ncomms2921. PMID 23715267.
^ 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. Mortensen, ME et al. (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome". Med Pediatr Oncol 20 (3): 249–253. PMID 1574039.

External links[edit]

Information from Macmillan Cancer Support
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English Journal

Targeted and controlled release delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer-modified gold nanoparticles.

Danesh NM1, Lavaee P2, Ramezani M3, Abnous K4, Taghdisi SM5.
International journal of pharmaceutics.Int J Pharm.2015 Jul 15;489(1-2):311-7. doi: 10.1016/j.ijpharm.2015.04.072. Epub 2015 Apr 29.
Clinical administration of daunorubicin (Dau) in treatment of leukemia has been limited by its cardiotoxicity. Targeted delivery of chemotherapy drugs could reduce their side effects and increase the therapeutic efficacy of these drugs. Biocompatibility and large surface area of gold nanoparticles (
PMID 25936625

Oral Debio1143 (AT406), an Antagonist of Inhibitor of Apoptosis Proteins, Combined With Daunorubicin and Cytarabine in Patients With Poor-Risk Acute Myeloid Leukemia-Results of a Phase I Dose-Escalation Study.

DiPersio JF1, Erba HP2, Larson RA3, Luger SM4, Tallman MS5, Brill JM6, Vuagniaux G7, Rouits E7, Sorensen JM6, Zanna C7.
Clinical lymphoma, myeloma & leukemia.Clin Lymphoma Myeloma Leuk.2015 Jul;15(7):443-9. doi: 10.1016/j.clml.2015.02.020. Epub 2015 Mar 5.
BACKGROUND: Treatment of acute myeloid leukemia (AML) remains difficult owing to the development of treatment resistance, which might be overcome through antagonists of inhibitors of apoptosis proteins (IAPs).PATIENTS AND METHODS: The present multicenter, open-label, dose-escalation study aimed to e
PMID 25842225

Characterization of the Canine Anthracycline-Metabolizing Enzyme Carbonyl Reductase 1 (cbr1) and the Functional Isoform cbr1 V218.

Ferguson DC1, Cheng Q1, Blanco JG2.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Jul;43(7):922-7. doi: 10.1124/dmd.115.064295. Epub 2015 Apr 27.
The anthracyclines doxorubicin and daunorubicin are used in the treatment of various human and canine cancers, but anthracycline-related cardiotoxicity limits their clinical utility. The formation of anthracycline C-13 alcohol metabolites (e.g., doxorubicinol and daunorubicinol) contributes to the d
PMID 25918240

Japanese Journal

キチン-キトサン膜で被覆された電極を用いるタンパク質-リガンド間結合の電気化学的評価

菅原一晴,由上麻子
分析化学 = Japan analyst 60(4), 353-356, 2011-04-05
… To evaluate the binding on the film, biotin labeled with an electroactive daunomycin was used as a probe. …
NAID 10028107116

Biodegradation of Daunomycin Post-Production Wastes by Bjerkandera Adusta R59

Cho Nam-Seok,Kornillowiczcarz Kowalska,Ginalska Grazyna,Cho Hee-Yeon,Shin Soo-Jeong,Ohga Shoji,大賀祥治
Journal of the Faculty of Agriculture, Kyushu University 54(2), 279-284, 2009-10-29
… Wastes from industrial production of daunomycin belong to strongly toxic and recalcitrant substances. … This study was investigated to the potential use of Bjerkandera adusta R59 as inoculum in process of daunomycin degradation in soil. … Process of degradation of daunomycin post-production wastes in soil was described. …
NAID 120001766548

Decolorization and Degradation of Daunomycin by Bjerkandera adusta R59 Strain

Cho Nam-Seok,Belearz Anna,Ginalska Grazyna,Kornillowicz Kowalska,Cho Hee-Yeon,Ohga Shoji,大賀祥治
Journal of the Faculty of Agriculture, Kyushu University 54(1), 65-71, 2009-02-27
… The ability of Bjerkandera adusta R59 strain to degrade anthraquinonic antibiotic (daunomycin) points on its possible aptitudes for decomposing of other anthraquinonic derivatives, e.g. lignocellulose subunits or metabolically related lipids, present in wood. … It was found to completely decolorize and degrade 10% daunomycin post-production effluent during 10 days of incubation at 26℃. …
NAID 120001204016

Related Pictures

★リンクテーブル★

リンク元	「ダウノルビシン」「daunorubicin hydrochloride」

「ダウノルビシン」

Daunorubicin
Systematic (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
Clinical data
Trade names	Cerubidine
AHFS/Drugs.com	monograph
MedlinePlus	a682289
Pregnancy cat.	D (U.S.)
Legal status	℞-only (US)
Routes	Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously
Pharmacokinetic data
Metabolism	Hepatic
Half-life	26.7 hours (metabolite)
Excretion	Biliary and urinary
Identifiers
CAS number	20830-81-3
ATC code	L01DB02
PubChem	CID 30323
DrugBank	DB00694
ChemSpider	28163
UNII	ZS7284E0ZP
KEGG	C01907
ChEBI	CHEBI:41977
ChEMBL	CHEMBL178
Chemical data
Formula	C27H29NO10
Mol. mass	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;
	InChI InChI=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 ; Key:STQGQHZAVUOBTE-VGBVRHCVSA-N ;
(what is this?) (verify);

　　[★]

英: daunorubicin DNR
同: ルビドマイシン rubidomycin
化: 塩酸ダウノルビシン daunorubicin hydrochloride
商: ダウノマイシン daunomycin、cerubidine, daunoxome
関

「daunorubicin hydrochloride」

　　[★]

塩酸ダウノルビシン

関: daunomycin、daunorubicin

[weiss-1] Weiss RB (December 1992). "The anthracyclines: will we ever find a better doxorubicin?". Seminars in Oncology 19 (6): 670–86. PMID 1462166.

[TanC-2] Tan C, Tasaka H, Yu KP, Murphy ML, Karnofsky DA (March 1967). "Daunomycin, an antitumor antibiotic, in the treatment of neoplastic disease. Clinical evaluation with special reference to childhood leukemia". Cancer 20 (3): 333–53. doi:10.1002/1097-0142(1967)20:3<333::AID-CNCR2820200302>3.0.CO;2-K. PMID 4290058.

[3] ttp://www.rcsb.org/pdb/explore.do?structureId=1D12

[fornari-4] Fornari FA, Randolph JK, Yalowich JC, Ritke MK, Gewirtz DA (April 1994). "Interference by doxorubicin with DNA unwinding in MCF-7 breast tumor cells". Mol Pharmacol 45 (4): 649–56. PMID 8183243.

[momparler-5] Momparler RL, Karon M, Siegel SE, Avila F (August 1976). "Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells". Cancer Res 36 (8): 2891–5. PMID 1277199.

[6] G J Quigley, A H Wang, G Ughetto, G van der Marel, J H van Boom, and A Rich (December 1980). "Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG)". PNAS 77 (12): 7204–7208.

[Pang-7] 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 (2013). "Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin". Nature Communications 4: 1908. doi:10.1038/ncomms2921. PMID 23715267.

[8] 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. Mortensen, ME et al. (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome". Med Pediatr Oncol 20 (3): 249–253. PMID 1574039.

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案内

daunomycin