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Daunorubicin or daunomycin (trade name 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 leukemia (acute myeloid leukemia and acute lymphocytic leukemia). It was initially isolated from Streptomyces peucetius.

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

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[1]

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 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

Similar to Doxorubicin, Daunorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis.^[2]^[3] 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 8°, but negligible distortion of helical conformation.^[4] It can also induce histone eviction from chromatin upon intercalation.^[5]

History

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.^[6] 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.^[7]

Route of administration

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. 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.^[8]

References

^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ 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. doi:10.1073/pnas.77.12.7204.
^ 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.
^ 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.
^ Mortensen, ME; et al. (1992). "Inadvertent intrathecal injection of daunorubicin with fatal outcome". Med Pediatr Oncol 20 (3): 249–253. PMID 1574039. External link in |journal= (help)

External links

Information from Macmillan Cancer Support
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UpToDate Contents

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English Journal

Oxime bond-linked daunorubicin-GnRH-III bioconjugates exert antitumor activity in castration-resistant prostate cancer cells via the type I GnRH receptor.

Montagnani Marelli M1, Manea M2, Moretti RM1, Marzagalli M1, Limonta P1.
International journal of oncology.Int J Oncol.2015 Jan;46(1):243-53. doi: 10.3892/ijo.2014.2730. Epub 2014 Oct 24.
It is well established that gonadotropin-releasing hormone receptors (GnRH-R) are expressed in different types of cancers, including castration-resistant prostate cancer (CRPC) and mediate the antiproliferative effect of GnRH analogs. Thus, these compounds are employed as targeting moieties to selec
PMID 25351635

Efficacy of CPX-351, (cytarabine:daunorubicin) liposome injection, against acute lymphoblastic leukemia (ALL) xenograft models of the Pediatric Preclinical Testing Program.

Carol H1, Fan MM, Harasym TO, Boehm I, Mayer LD, Houghton P, Smith MA, Lock RB.
Pediatric blood & cancer.Pediatr Blood Cancer.2015 Jan;62(1):65-71. doi: 10.1002/pbc.25133. Epub 2014 Sep 9.
BACKGROUND: CPX-351, a liposomal formulation of cytarabine and daunorubicin co-encapsulated at an optimized synergistic 5:1 molar ratio, has demonstrated improved clinical outcomes over conventional cytarabine/daunorubicin treatment in a randomized phase 2 trial in patients with AML as well as super
PMID 25203866

Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia.

De Astis E1, Clavio M, Raiola AM, Ghiso A, Guolo F, Minetto P, Galaverna F, Miglino M, Di Grazia C, Ballerini F, Marani C, Pastori G, Mitscheunig L, Cruciani F, Lovera D, Varaldo R, Ghiggi C, Lemoli RM, Bacigalupo A, Gobbi M.
Annals of hematology.Ann Hematol.2014 Dec;93(12):2011-8. doi: 10.1007/s00277-014-2143-8. Epub 2014 Jul 4.
Therapeutic options for patients with relapsed or refractory acute leukemia are still undefined and often unsatisfactory. We report the outcome of 79 patients with relapsed-refractory acute leukemia treated with fludarabine, cytarabine, and liposomal daunorubicin (FLAD regimen) followed by hematopoi
PMID 24989345

Japanese Journal

急性白血病の薬剤耐性とABCトランスポーター

泉二登志子/王艶華
東京女子医科大学雑誌 83(E2), E451-E457, 2013-03-31
急性白血病の治療成績は著しく向上してきたものの、抗がん薬に対する耐性が長期生存を妨げている。抗がん薬に対する薬剤耐性は複数の機序が重なって生じると考えられている。その代表的な機序であるABCトランスポーターは、multidrug resistance 1(MDR1)と産物であるP-glycprotein(P-gp)、ABCG2遺伝子とその産物であるbreast cancer related pro …
NAID 110009575051

Randomized comparison of fixed-schedule versus response-oriented individualized induction therapy and use of ubenimex during and after consolidation therapy for elderly patients with acute myeloid leukemia : the JALSG GML200 Study

WAKITA Atsushi,OHTAKE Shigeki,TAKADA Satoru,YAGASAKI Fumiharu,KOMATSU Hirokazu,MIYAZAKI Yasushi,KUBO Kohmei,KIMURA Yukihiko,TAKESHITA Akihiro,ADACHI Yoko,KIYOI Hitoshi,YAMAGUCHI Takuhiro,YOSHIDA Minoru,OHNISHI Kazunori,MIYAWAKI Shuichi,NAOE Tomoki,UEDA Ryuzo,OHNO Ryuzo
International journal of hematology 96(1), 84-93, 2012-07-01
NAID 10030954605

AMLに対する高用量daunorubicin (特集造血器腫瘍における高用量治療の評価)

薄井紀子
腫瘍内科 9(2), 163-170, 2012-02-00
NAID 40019216617

Related Pictures

★リンクテーブル★

リンク元	「イリノテカン」「アントラサイクリン」「ダウノルビシン」「cerubidine」
拡張検索	「daunorubicin hydrochloride」

「イリノテカン」

Daunorubicin (INN)
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; category	D (U.S.);
Legal status	US: ℞-only;
Routes of; administration	Exclusively intravenous. Causes severe necrosis if administered intramuscularly or subcutaneously
Pharmacokinetic data
Metabolism	Hepatic
Biological half-life	26.7 hours (metabolite)
Excretion	Biliary and urinary
Identifiers
CAS Number	20830-81-3
ATC code	L01DB02
PubChem	CID: 30323
IUPHAR/BPS	7063
DrugBank	DB00694
ChemSpider	28163
UNII	ZS7284E0ZP
KEGG	C01907
ChEBI	CHEBI:41977
ChEMBL	CHEMBL178
Chemical data
Formula	C27H29NO10
Molecular 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 ;
(verify)

　　[★]

英: irinotecan IRT, CPT-11
同: 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin]
化: 塩酸イリノテカン irinotecan hydrochloride、イリノテカン塩酸塩
商: カンプト、トポテシン
関: 抗悪性腫瘍薬; 抗腫瘍性植物成分製剤

概念

抗悪性腫瘍薬の一種。
camptothecinのアナログ

作用機序

トポイソメラーゼの機能を阻害してDNA合成を阻害する

block topoisomerase function

同じグループの薬剤

camptothecins

「アントラサイクリン」

　　[★]

英: anthracycline, anthracyclines
商: ダウノマイシン、アドリアシン
関: 抗悪性腫瘍薬

アントラサイクリン系抗悪性腫瘍薬

「ダウノルビシン」

　　[★]

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

「cerubidine」

　　[★]

同: daunorubicin hydrochloride

関: daunorubicin

「daunorubicin hydrochloride」

　　[★]

塩酸ダウノルビシン

関: daunomycin、daunorubicin

[WHO2015E-1] "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.

[fornari-2] 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-3] 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.

[4] 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. doi:10.1073/pnas.77.12.7204.

[Pang-5] 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.

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

[TanC-7] 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.

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

匿名

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案内

案内

daunorubicin