Guadecitabine (SGI-110)

製品コードS7013 バッチS701301

化学情報

	Synonyms	S-110	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₈ H₂₃ N₉ O₁₀ P . Na
	分子量	579.39	CAS No.	929904-85-8
Solubility (25°C)*	体外	DMSO	100 mg/mL (172.59 mM)
		Water	50 mg/mL (86.29 mM)
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Guadecitabine (SGI-110, S-110) is a next-generation hypomethylating agent whose active metabolite decitabine has a longer in-vivo exposure time than intravenous decitabine.
in vitro	SGI-110 is a 5-aza-2’-deoxycytidine-containing demethylating dinucleotide, which works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. However, SGI-110 is well protected from deamination by cytidine deaminase. SGI-110 (1 μM) induces significantly decrease in the level of methylation in both T24 and HCT116 cells. SGI-110 is able to induce robust p16 expression. SGI-110 (1 μM) causes depletion of extractable DNMT1 in cells. SGI-110 decreases the plating efficiency of T24 bladder carcinoma cells in a dose-dependent manner, with no colonies forming at 10 μM concentration, which is quite similar to 5-aza-CdR in T24 cells. ^[1] SGI-110 shows immunomodulatory activity in vitro. SGI-110 (1 μM) induces/up-regulates the expression of several cancer/testis antigens (CTA) (i.e., MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A10, GAGE1-2, GAGE 1-6, NY-ESO-1, and SSX 1-5) in cancer cell lines (cutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells), both at mRNA and at protein levels. SGI-110 also up-regulates the expression of HLA class I antigens and of ICAM-1, resulting in an improved recognition of cancer cells by gp100-specific CTL. ^[2]
in vivo	SGI-110 is as effective as 5-Aza-CdR, but is better tolerated in mice. SGI-110 (10 mg/kg) displays potent activity on inducing p16 expression, reducing DNA methylation at the p16 promoter region, and retarding tumor growth in human xenograft. SGI-110 is effective by both i.p. and s.c. deliveries. ^[3]

製品説明

Guadecitabine (SGI-110, S-110) is a next-generation hypomethylating agent whose active metabolite decitabine has a longer in-vivo exposure time than intravenous decitabine.

in vitro

SGI-110 is a 5-aza-2’-deoxycytidine-containing demethylating dinucleotide, which works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. However, SGI-110 is well protected from deamination by cytidine deaminase. SGI-110 (1 μM) induces significantly decrease in the level of methylation in both T24 and HCT116 cells. SGI-110 is able to induce robust p16 expression. SGI-110 (1 μM) causes depletion of extractable DNMT1 in cells. SGI-110 decreases the plating efficiency of T24 bladder carcinoma cells in a dose-dependent manner, with no colonies forming at 10 μM concentration, which is quite similar to 5-aza-CdR in T24 cells. ^[1]

SGI-110 shows immunomodulatory activity in vitro. SGI-110 (1 μM) induces/up-regulates the expression of several cancer/testis antigens (CTA) (i.e., MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A10, GAGE1-2, GAGE 1-6, NY-ESO-1, and SSX 1-5) in cancer cell lines (cutaneous melanoma, mesothelioma, renal cell carcinoma, and sarcoma cells), both at mRNA and at protein levels. SGI-110 also up-regulates the expression of HLA class I antigens and of ICAM-1, resulting in an improved recognition of cancer cells by gp100-specific CTL. ^[2]

in vivo

SGI-110 is as effective as 5-Aza-CdR, but is better tolerated in mice. SGI-110 (10 mg/kg) displays potent activity on inducing p16 expression, reducing DNA methylation at the p16 promoter region, and retarding tumor growth in human xenograft. SGI-110 is effective by both i.p. and s.c. deliveries. ^[3]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	UMUC-3 cells
	濃度	2 μM
	反応時間	24 h
	実験の流れ	Cells were treated with indicated concentrations of drug.
動物実験	動物モデル	Human bladder cancers xenografts EJ6
	投薬量	10 mg/kg
	投与方法	i.p. or s.c.

参考

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Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

DNA methyltransferase inhibition promotes recruitment of myeloid-derived suppressor cells to the tumor microenvironment through induction of tumor cell-intrinsic interleukin-1 [ Cancer Lett, 2023, 552:215982]	PubMed: 36309209
DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway [ Cancers (Basel), 2023, 15(10)2763]	PubMed: 37345101
DNA methylation subtypes guiding prognostic assessment and linking to responses the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma [ BMC Med, 2022, 20(1):222]	PubMed: 35843958
Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors [ Mol Cancer Ther, 2021, 20(12):2362-2371]	PubMed: 34552007
Growth Inhibition and Induction of Innate Immune Signaling of Chondrosarcomas with Epigenetic Inhibitors [ Mol Cancer Ther, 2021, molcanther.MCT-21-0066-A.2021]	PubMed: 34552007
Smac mimetics and TRAIL cooperate to induce MLKL-dependent necroptosis in Burkitt's lymphoma cell lines [ Neoplasia, 2021, 23(5):539-550]	PubMed: 33971465
Epigenetic repression of miR-375 is the dominant mechanism for constitutive activation of the PDPK1/RPS6KA3 signalling axis in multiple myeloma [ Br J Haematol, 2017, 178(4):534-546]	PubMed: 28439875

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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