5-Aza-2'-deoxycytidine

Bezeichnung:5-Aza-2'-deoxycytidine

CAS-Nr2353-33-5

Englisch Name:5-Aza-2'-deoxycytidine

CBNumberCB6284800

SummenformelC8H12N4O4

Molgewicht228.21

MOL-Datei2353-33-5.mol

5-Aza-2'-deoxycytidine physikalisch-chemischer Eigenschaften

Schmelzpunkt	~200 °C (dec.)
alpha	D22 +68.5° (30 min) +57.8° (6 hr) (c = 0.5 in water)
Siedepunkt	370.01°C (rough estimate)
Dichte	1.3771 (rough estimate)
Brechungsindex	1.6590 (estimate)
storage temp.	Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
Löslichkeit	acetic acid/water (1:1): 50 mg/mL
pka	14.02±0.60(Predicted)
Aggregatzustand	Powder
Farbe	White to Off-white
Merck	14,2853
BRN	617982
Stabilität	Stable. May be light or air sensitive. Incompatible with strong oxidizing agents.
InChIKey	XAUDJQYHKZQPEU-KVQBGUIXSA-N
CAS Datenbank	2353-33-5(CAS DataBase Reference)
EPA chemische Informationen	5-Aza-2'-deoxycytidine (2353-33-5)

Sicherheit

Kennzeichnung gefährlicher	Xn,Xi,T
R-Sätze:	22-36/37/38-68-61
S-Sätze:	26-36-36/37
WGK Germany	3
RTECS-Nr.	XZ3012000
F	10-34
HS Code	29349990
Toxizität	LD50 in mice (mg/kg): 190 i.p. (Momparler, 1985)

Gefahreninformationscode (GHS)

5-Aza-2'-deoxycytidine Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Decitabine, 5-aza-2’-deoxycytidine, has been launched for the treatment of myelodysplastic syndromes (MDS). MDS are a set of hematologic disorders affecting the bone marrow that result in ineffective formation and development of blood cells. Furthermore, patients with MDS have a high risk of progressing to acute myeloid leukemia (AML). Traditional treatments include blood transfusions, hematopoietic growth factors, and prophylactic antibiotics, but these measures merely improve the quality of life with questionable effects on disease modification. While stem-cell transplantation is an aggressive, potentially curative approach, the advanced age or the other complicating health issues of most patients preclude them from considering this option. Recent advances in the underlying etiology of MDS, however, have led to the development of a new class of compounds known as ‘‘demethylating agents’’. Decitabine follows the successful introduction of the first DNA methyltransferase inhibitor azacitidine.
Chemische Eigenschaften
white crystalline powder
Originator
Pharmachemie (Netherlands)
Verwenden
Decitabine is a potent inhibitor of DNA methylation with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively
Verwenden
5-Aza-2′-deoxycytidine has been used as a demethylating agent in breast cancer cell line, chromatin, DNA and promoter region of p16 gene.
Verwenden
Used as cancer treatment, in particular to inhibit the growth of pancreatic endocrine tumor cell lines.
Definition
ChEBI: 5-aza-2'-deoxycytidine is a 2'-deoxyribonucleoside.
Trademarks
Dacogen (Millot Laboratories, France).
Allgemeine Beschreibung
Fine white crystalline powder. Used as a drug.
Air & Water Reaktionen
Probably light and air sensitive. Water soluble. Decomposes in aqueous solution at a rate that depends on pH: at pH 7 the drug is more stable than at pH 9, but is less stable than at pH 6. At pH 7 and 99°F, approximately 7% conversion occurs in 1 hour .
Reaktivität anzeigen
5-Aza-2'-deoxycytidine is an aminoalcohol. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.
Brandgefahr
Flash point data for 5-Aza-2'-deoxycytidine are not available. 5-Aza-2'-deoxycytidine is probably combustible.
Biologische Aktivität
Cytosine analog that once incorporated into DNA acts as a suicide substrate for DNA methyltransferase. Inhibits DNA methyltransferase and results in DNA hypomethylation and activation of silent genes. Chemotherapeutic agent; suppresses growth of human tumor cell lines. Demethylates differentiation-related genes; reverses embryonic stem cell differentiation.
Biochem/physiol Actions
Primary TargetDNA methyltransferase inhibitor
Clinical Use
Antineoplastic antimetabolite agent:
Treatment of acute myeloid leukaemia
Sicherheitsprofil
Poison by intravenous route.Human mutation data reported. When heated todecomposition it emits toxic fumes of NOx.
Synthese
Silylated 5-aza-cytosine (28) was condensed with 9- fluorenylmethoxycarbonyl (Fmoc) protected 2-deoxy-1-chlororibose (27) with tin chloride (IV) in dichloroethane (Scheme 4). The coupled product 29 was de-protected with excess triethylamine in dry pyridine to give decitabine (IV) in 36% yield after separation from its corresponding |áisomer.
target
Telomerase | DNA Methyltransferase | p21
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine, increased risk of agranulocytosis.
Stoffwechsel
The exact route of metabolism and elimination is unknown but thought to be through deamination by cytidine deaminase in the liver, kidney, intestinal epithelium and blood to form inactive metabolites.
Lager
+4°C
Einzelnachweise
1) Bender et al. (1998), Inhibition of DNA methylation by 5-aza-2′-deoxycytidine suppresses the growth of human tumor cell lines; Cancer Res., 58 95 2) El-Serafi et al. (2011), Epigenetic modifiers influence lineage commitment of human bone marrow stromal cells: Differential effects of 5-aza-deoxycytidine and trichostatin A; Differentiation, 81 35

5-Aza-2'-deoxycytidine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

2353-33-5, 5-Aza-2'-deoxycytidine Verwandte Suche:

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