Azacitidine | CAS#320-67-2 | DNA methylation

MedKoo Cat#: 100070 | Name: Azacitidine

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic activity. Azacitidine is incorporated into DNA, where it reversibly inhibits DNA methyltransferase, thereby blocking DNA methylation. Hypomethylation of DNA by azacitidine may activate tumor suppressor genes silenced by hypermethylation, resulting in an antitumor effect. This agent is also incorporated into RNA, thereby disrupting normal RNA function and impairing tRNA cytosine-5-methyltransferase activity.

Chemical Structure

Azacitidine

CAS#320-67-2

Theoretical Analysis

MedKoo Cat#: 100070

Name: Azacitidine

CAS#: 320-67-2

Chemical Formula: C8H12N4O5

Exact Mass: 244.0808

Molecular Weight: 244.20

Elemental Analysis: C, 39.35; H, 4.95; N, 22.94; O, 32.76

Price and Availability

Size	Price	Availability
1g	USD 90.00	Ready to ship
2g	USD 150.00	Ready to ship
5g	USD 250.00	Ready to ship
10g	USD 450.00	2 weeks
20g	USD 750.00	2 Weeks

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Related CAS #

No Data

Synonym

U18496; U-18496; U 18496; Abbreviations: 5AC; 5AZC. 5-azacytidine; azacytidine; ladakamycin. US brand names: Mylosar; Vidaza.

IUPAC/Chemical Name

4-amino-1-((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-1,3,5-triazin-2(1H)-one

InChi Key

NMUSYJAQQFHJEW-KVTDHHQDSA-N

InChi Code

InChI=1S/C8H12N4O5/c9-7-10-2-12(8(16)11-7)6-5(15)4(14)3(1-13)17-6/h2-6,13-15H,1H2,(H2,9,11,16)/t3-,4-,5-,6-/m1/s1

SMILES Code

O=C1N([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)C=NC(N)=N1

Appearance

white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>10 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

According to http://en.wikipedia.org/wiki/Azacitidine, Azacitidine is mainly used in the treatment of myelodysplastic syndrome (MDS), for which it received approval by the U.S. Food and Drug Administration on May 19, 2004; it is marketed as Vidaza. In a randomized controlled trial comparing azacitidine to supportive treatment of MDS, around 16% of people receiving the drug had a complete or partial responseÂ—blood cell counts and bone marrow morphology returning to normalÂ—and 2/3 patients who required blood transfusions before the study no longer needed them after receiving azacitidine. It can also be used in vitro to remove methyl groups from DNA. This may weaken the effects of gene silencing mechanisms that occurred prior to the methylation. Methylation events are therefore believed to secure the DNA in a silenced state. Demethylation may reduce the stability of silencing signals and thus confer relative gene activation. DRUG DESCRIPTION VIDAZA (azacitidine for injection) contains azacitidine, which is a pyrimidine nucleoside analog of cytidine. Azacitidine is 4-amino-1-β-D-ribofuranosyl-s-triazin-2(1H)-one. The empirical formula is C8H12N4O5. The molecular weight is 244. Azacitidine is a white to off- white solid. Azacitidine was found to be insoluble in acetone, ethanol, and methyl ethyl ketone; slightly soluble in ethanol/water (50/50), propylene glycol, and polyethylene glycol; sparingly soluble in water, water saturated octanol, 5% dextrose in water, N-methyl-2-pyrrolidone, normal saline and 5% Tween 80 in water; and soluble in dimethylsulfoxide (DMSO). The finished product is supplied in a sterile form for reconstitution as a suspension for subcutaneous injection or reconstitution as a solution with further dilution for intravenous infusion. Vials of VIDAZA contain 100 mg of azacitidine and 100 mg mannitol as a sterile lyophilized powder. Mechanism of Action VIDAZA is a pyrimidine nucleoside analog of cytidine. VIDAZA is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylationin vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#YYP30917

QC Data

View QC data: current batch, Lot#YYP30917

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Azacitidine (5-Azacytidine, 5-AzaC, Ladakamycin, AZA, 5-Aza, CC-486) is a nucleoside analogue of cytidine that specifically inhibits DNA methylation by trapping DNA methyltransferases.

In vitro activity:

To test whether efficient DNA demethylation is indeed critical for the induction of stable Foxp3 expression in vitro, DNA-hypomethylating Aza (azacitidine, 5-azacytidine or 5-aza-deoxycytidine) was used to interfere with de novo DNA methylation. During replication these nucleoside analogs are integrated into DNA (and RNA for 5-azacytidine) and subsequently interfere with the function of DNMT1 (DNA methyltransferase 1) leading to rapid passive DNA demethylation. To test the impact of DNA methylation on the stability of Foxp3 expression, Treg was first indued in vitro by activation of Foxp3–CD25–CD4+ T cells in the presence of TGF-β. After sorting of Foxp3+ iTreg to high purity (97%), cells were restimulated either alone or in the presence of TGF-β or Aza. As depicted in Fig. 2, Aza significantly increased the proportion of cells expressing Foxp3 compared to restimulation cultures without exogenous TGF-β and Aza, which rapidly lost Foxp3 expression over time (Fig. 2B). On day 4 of restimulation, the percentage of Foxp3+ cells in Aza-treated cultures was more than 4-fold increased (Fig. 2A, 47% and 9.3% cells maintained Foxp3 expression in Aza-treated and non-treated cultures, respectively). TGF-β-containing control cultures maintained high Foxp3 expression with 91% Foxp3+ cells on day 4 (Fig. 2A). These results strengthen the idea of an essential role for DNA (de)methylation in the regulation of Foxp3 stability. Reference: Eur J Immunol. 2008 Jun;38(6):1654-63. https://doi.org/10.1002/eji.200838105

In vivo activity:

Immunocompetent C57BL/6 mice were injected intraperitoneally (i.p.) with 250,000 VDID8 syngeneic MOSE cells. Mice were treated IP with azacitidine (AZA) (0.5 mg/kg). Hemorrhagic ascites fluid consistently develops at approximately 4–5 weeks post VDID8 injection and is an accurate measurement of tumor burden in mice, allowing observation of tumor growth in real time. After draining hemorrhagic ascites fluid from mice for the second time (typically week 5 post tumor injection), mice treated with single agent AZA demonstrated significantly lower tumor burdens (Fig 1b). Mice treated with AZA had an increase in median survival of 44 days (Fig 1c). Total numbers of lymphocytes are significantly increased by single agent AZA (Fig 1d,,ee). AZA led to significant increases in T cell, NK cell, and IFNγ+ lymphocyte populations examined in the tumor microenvironment (Fig 2a–g). Reference: Cancer Res. 2019 Jul 1;79(13):3445-3454. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31088836/

	Solvent	mg/mL	mM
Solubility
	DMSO	31.0	126.95
	Water	33.3	136.49

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 244.20 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Polansky JK, Kretschmer K, Freyer J, Floess S, Garbe A, Baron U, Olek S, Hamann A, von Boehmer H, Huehn J. DNA methylation controls Foxp3 gene expression. Eur J Immunol. 2008 Jun;38(6):1654-63. doi: 10.1002/eji.200838105. PMID: 18493985. 2. Osorio-Montalvo P, Sáenz-Carbonell L, De-la-Peña C. 5-Azacytidine: A Promoter of Epigenetic Changes in the Quest to Improve Plant Somatic Embryogenesis. Int J Mol Sci. 2018 Oct 16;19(10):3182. doi: 10.3390/ijms19103182. PMID: 30332727; PMCID: PMC6214027.

In vivo protocol:

1. Travers M, Brown SM, Dunworth M, Holbert CE, Wiehagen KR, Bachman KE, Foley JR, Stone ML, Baylin SB, Casero RA Jr, Zahnow CA. DFMO and 5-Azacytidine Increase M1 Macrophages in the Tumor Microenvironment of Murine Ovarian Cancer. Cancer Res. 2019 Jul 1;79(13):3445-3454. doi: 10.1158/0008-5472.CAN-18-4018. Epub 2019 May 14. PMID: 31088836; PMCID: PMC6606334.

1: Pollyea DA, Winters A, McMahon C, Schwartz M, Jordan CT, Rabinovitch R, Abbott D, Smith CA, Gutman JA. Venetoclax and azacitidine followed by allogeneic transplant results in excellent outcomes and may improve outcomes versus maintenance therapy among newly diagnosed AML patients older than 60. Bone Marrow Transplant. 2022 Feb;57(2):160-166. doi: 10.1038/s41409-021-01476-7. Epub 2021 Oct 13. PMID: 34645926. 2: Azacitidine. IARC Monogr Eval Carcinog Risks Hum. 1990;50:47-63. PMID: 1705587; PMCID: PMC7681440. 3: Müller A, Florek M. 5-Azacytidine/Azacitidine. Recent Results Cancer Res. 2010;184:159-70. doi: 10.1007/978-3-642-01222-8_11. PMID: 20072837. 4: Issa JP, Kantarjian HM, Kirkpatrick P. Azacitidine. Nat Rev Drug Discov. 2005 Apr;4(4):275-6. doi: 10.1038/nrd1698. PMID: 15861567. 5: Siddiqui MA, Scott LJ. Azacitidine: in myelodysplastic syndromes. Drugs. 2005;65(13):1781-9; discussion 1790-1. doi: 10.2165/00003495-200565130-00004. PMID: 16114977. 6: Cogle CR, Scott BL, Boyd T, Garcia-Manero G. Oral Azacitidine (CC-486) for the Treatment of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Oncologist. 2015 Dec;20(12):1404-12. doi: 10.1634/theoncologist.2015-0165. Epub 2015 Oct 13. PMID: 26463870; PMCID: PMC4679081. 7: Sullivan M, Hahn K, Kolesar JM. Azacitidine: a novel agent for myelodysplastic syndromes. Am J Health Syst Pharm. 2005 Aug 1;62(15):1567-73. doi: 10.2146/ajhp040385. PMID: 16030365. 8: Cataldo VD, Cortes J, Quintás-Cardama A. Azacitidine for the treatment of myelodysplastic syndrome. Expert Rev Anticancer Ther. 2009 Jul;9(7):875-84. doi: 10.1586/era.09.61. PMID: 19589026. 9: O'Dwyer K, Maslak P. Azacitidine and the beginnings of therapeutic epigenetic modulation. Expert Opin Pharmacother. 2008 Aug;9(11):1981-6. doi: 10.1517/14656566.9.11.1981. PMID: 18627335. 10: Abdulhaq H, Rossetti JM. The role of azacitidine in the treatment of myelodysplastic syndromes. Expert Opin Investig Drugs. 2007 Dec;16(12):1967-75. doi: 10.1517/13543784.16.12.1967. PMID: 18042004. 11: Santini V. Azacitidine: activity and efficacy as an epigenetic treatment of myelodysplastic syndromes. Expert Rev Hematol. 2009 Apr;2(2):121-7. doi: 10.1586/ehm.09.6. PMID: 21083445. 12: Götze K, Platzbecker U, Giagounidis A, Haase D, Lübbert M, Aul C, Ganser A, Germing U, Hofmann WK. Azacitidine for treatment of patients with myelodysplastic syndromes (MDS): practical recommendations of the German MDS Study Group. Ann Hematol. 2010 Sep;89(9):841-50. doi: 10.1007/s00277-010-1015-0. Epub 2010 Jun 22. PMID: 20567826. 13: Vigil CE, Martin-Santos T, Garcia-Manero G. Safety and efficacy of azacitidine in myelodysplastic syndromes. Drug Des Devel Ther. 2010 Sep 24;4:221-9. doi: 10.2147/dddt.s3143. PMID: 20957213; PMCID: PMC2948932. 14: Glover AB, Leyland-Jones B. Biochemistry of azacitidine: a review. Cancer Treat Rep. 1987 Oct;71(10):959-64. PMID: 2443243. 15: Xie M, Jiang Q, Xie Y. Comparison between decitabine and azacitidine for the treatment of myelodysplastic syndrome: a meta-analysis with 1,392 participants. Clin Lymphoma Myeloma Leuk. 2015 Jan;15(1):22-8. doi: 10.1016/j.clml.2014.04.010. Epub 2014 Jun 12. PMID: 25042977. 16: Glover AB, Leyland-Jones BR, Chun HG, Davies B, Hoth DF. Azacitidine: 10 years later. Cancer Treat Rep. 1987 Jul-Aug;71(7-8):737-46. PMID: 2440570. 17: Morimoto Y, Chonabayashi K, Kawabata H, Okubo C, Yamasaki-Morita M, Nishikawa M, Narita M, Inagaki A, Nakanishi K, Nagao M, Takaori-Kondo A, Yoshida Y. Azacitidine is a potential therapeutic drug for pyridoxine-refractory female X-linked sideroblastic anemia. Blood Adv. 2022 Feb 22;6(4):1100-1114. doi: 10.1182/bloodadvances.2021005664. PMID: 34781359; PMCID: PMC8864662. 18: Seelan RS, Mukhopadhyay P, Pisano MM, Greene RM. Effects of 5-Aza-2'-deoxycytidine (decitabine) on gene expression. Drug Metab Rev. 2018 May;50(2):193-207. doi: 10.1080/03602532.2018.1437446. Epub 2018 Feb 18. PMID: 29455551. 19: Adès L, Itzykson R, Fenaux P. Treatment of advanced myelodysplastic syndrome with demethylating agents: azacitidine. Semin Hematol. 2012 Oct;49(4):323-9. doi: 10.1053/j.seminhematol.2012.09.002. PMID: 23079062. 20: Yoshihiro T, Muta T, Aoki K, Shimamoto S, Tamura Y, Ogawa R. [Efficacy and adverse events of azacitidine in the treatment of hemodialysis patients with high-risk myelodysplastic syndrome]. Rinsho Ketsueki. 2016 Aug;57(8):1004-10. Japanese. doi: 10.11406/rinketsu.57.1004. PMID: 27599416.