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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/12/29 20:50:04」(JST)

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Decitabine (trade name Dacogen), or 5-aza-2'-deoxycytidine, is a drug for the treatment of myelodysplastic syndromes, a class of conditions where certain blood cells are dysfunctional, and for acute myeloid leukemia (AML).^[1] Chemically, it is a cytidine analog.

Mechanism

Decitabine is a hypomethylating agent.^[2]^[3] It hypomethylates DNA by inhibiting DNA methyltransferase.

It functions in a similar manner to azacitidine, although decitabine can only be incorporated into DNA strands while azacitidine can be incorporated into both DNA and RNA chains.

Clinical uses

Decitabine is indicated for the treatment of myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System groups. In patients with renal insufficiency, Batty and colleagues reported the first case series on the feasibility of therapy with hypomethylating agents in patients with renal insufficiency.^[4]

Chemical synthesis

Decitabine can be synthesized from a benzoyl-protected chlorosugar:^[5]

References

^ "EC Approves Marketing Authorization Of DACOGEN For Acute Myeloid Leukemia". 2012-09-28. Retrieved 28 September 2012.
^ Kantarjian H, Issa JP, Rosenfeld CS, et al. (April 2006). "Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study". Cancer 106 (8): 1794–1803. doi:10.1002/cncr.21792. PMID 16532500.
^ Kantarjian HM, O'Brien S, Cortes J, et al. (August 2003). "Results of decitabine (5-aza-2'deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia". Cancer 98 (3): 522–528. doi:10.1002/cncr.11543. PMID 12879469.
^ Ravandi, F.; Kantarjian, J. E.; Issa, S.; Jabbour, S.; Santos, G.; McCue, D.; Garcia-Manero, F. P. S.; Pierce, E.; O'Brien, J. P.; Cortés, J. E.; Ravandi, F. (2010). "Feasibility of Therapy with Hypomethylating Agents in Patients with Renal Insufficiency". Clinical Lymphoma, Myeloma & Leukemia 10 (3): 205–210. doi:10.3816/CLML.2010.n.032. PMC 3726276. PMID 20511166. edit
^ Piml, J.; Sorm, F. (1964). Coll. Czech. Chem. Commun. 29: 2576.

External links

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UpToDate Contents

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1. 高齢者における急性骨髄性白血病の治療 treatment of acute myeloid leukemia in older adults
2. 中等度～低リスクまたは極めて低リスクの骨髄異形成症候群の治療 treatment of intermediate low or very low risk myelodysplastic syndromes
3. 高リスクまたは極めて高リスクの骨髄異形成症候群の治療 treatment of high or very high risk myelodysplastic syndromes
4. 慢性骨髄単球性白血病 chronic myelomonocytic leukemia
5. 鎌状赤血球症に対するヒドロキシ尿素治療または疾患修飾療法 hydroxyurea and other disease modifying therapies in sickle cell disease

English Journal

Update on the pharmacotherapy for myelodysplastic syndromes.

Duong VH1, Komrokji RS, List AF.
Expert opinion on pharmacotherapy.Expert Opin Pharmacother.2014 Sep;15(13):1811-25. doi: 10.1517/14656566.2014.937705. Epub 2014 Jul 31.
INTRODUCTION: For many decades, myelodysplastic syndromes (MDS) were a poorly understood disease group with no approved therapies, and patient management largely relied upon supportive care and intensive chemotherapy. The last decade has seen many scientific and therapeutic advances culminating in t
PMID 25080144

Decitabine reduces transfusion dependence in older patients with acute myeloid leukaemia: results from a post-hoc analysis of a RANDOMISED Phase III study.

He J, Xiu L, De Porre P, Dass R, Thomas X.
Leukemia & lymphoma.Leuk Lymphoma.2014 Aug 7:1-22. [Epub ahead of print]
ABSTRACT This post-hoc analysis of the DACO-016 Phase III study evaluates the impact of decitabine on transfusion dependence and survival in 485 elderly patients with newly diagnosed acute myeloid leukemia (AML). Red blood cell (RBC) and platelet (PLT) transfusion independence, defined as no transfu
PMID 25098427

Epigenetic drugs against cancer: an evolving landscape.

Di Costanzo A1, Del Gaudio N, Migliaccio A, Altucci L.
Archives of toxicology.Arch Toxicol.2014 Aug 2. [Epub ahead of print]
Alteration of the chromatin orchestra seems to play a critical role in cancer. In recent years, in-depth studies of epigenetic machinery and its deregulation have led to the development and use of a wide range of modulatory molecules directed not only at chromatin enzymes (histone acetyltransferases
PMID 25085708

Japanese Journal

Cellular Uptake of Decitabine by Equilibrative Nucleoside Transporters in HCT116 Cells

Ueda Kumiko,Hosokawa Mika,Iwakawa Seigo
Biological and Pharmaceutical Bulletin 38(8), 1113-1119, 2015
… Decitabine (DAC), a DNA methyltransferase 1 inhibitor of nucleoside analogues, has been shown to restore gene expression silenced by hypermethylation. …
NAID 130005090657

Effects of Decitabine on Invasion and Exosomal Expression of miR-200c and miR-141 in Oxaliplatin-Resistant Colorectal Cancer Cells

Tanaka Shota,Hosokawa Mika,Ueda Kumiko,Iwakawa Seigo
Biological and Pharmaceutical Bulletin advpub(0), 2015
… The effects of decitabine (DAC), a DNA methyltransferase (DNMT) inhibitor, on metastasis and exosomal expression of microRNAs were examined in SW620/OxR cells, a human colorectal cancer (CRC) cell line (SW620) with acquired resistance to oxaliplatin. …
NAID 130005088147

Expression of myeloperoxidase in acute myeloid leukemia blasts mirrors the distinct DNA methylation pattern involving the downregulation of DNA methyltransferase DNMT3B

Itonaga Hidehiro,Imanishi Daisuke,Wong Yan-Fung,Sato Shinya,Ando Koji,Sawayama Yasushi,Sasaki Daisuke,Tsuruda Kazuto,Hasegawa Hiroo,Imaizumi Yoshitaka,Taguchi Jun,Tsushima Hideki,Yoshida Shinichiro,Fukushima Takuya,Hata Tomoko,Moriuchi Yukiyoshi,Yanagihara Katsunori,Miyazaki Yasushi
Leukemia 28(7), 1459-1466, 2014-07
… DNA methyltransferase inhibitors (decitabine and zeburaline) induced MPO gene promoter demethylation and MPO gene transcription in AML cells with low MPO activity. …
NAID 120005477053

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★リンクテーブル★

リンク元	「デシタビン」「5-aza-2'-deoxycytidine」

「デシタビン」

Decitabine
Systematic (IUPAC) name
	4-Amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
Clinical data
Trade names	Dacogen
AHFS/Drugs.com	monograph
MedlinePlus	a608009
Pregnancy cat.	D;
Legal status	℞ Prescription only;
Routes	Intravenous
Pharmacokinetic data
Protein binding	<1%
Half-life	30 minutes
Identifiers
CAS number	2353-33-5
ATC code	L01BC08
PubChem	CID 451668
DrugBank	DB01262
ChemSpider	397844
UNII	776B62CQ27
KEGG	D03665
ChEBI	CHEBI:50131
ChEMBL	CHEMBL1201129
Chemical data
Formula	C8H12N4O4
Mol. mass	228.206 g/mol
	SMILES O=C1/N=C(\N=C/N1[C@@H]2O[C@@H]([C@@H](O)C2)CO)N;
	InChI InChI=1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1 ; Key:XAUDJQYHKZQPEU-KVQBGUIXSA-N ;
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