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) は、その活性代謝物であるデシタビンが静脈内デシタビンよりも長い生体内曝露時間を有する次世代の低メチル化剤です。
in vitro	Guadecitabine (SGI-110) is a 5-aza-2′-deoxycytidine-containing demethylating dinucleotide that works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. However, it is well protected from deamination by cytidine deaminase. This compound (1 μM) induces a significant decrease in the level of methylation in both T24 and HCT116 cells and is able to induce robust p16 expression. It also causes depletion of extractable DNMT1 in cells at 1 μM concentration. Furthermore, it 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. It shows immunomodulatory activity in vitro. At 1 μM, it 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. This compound also up-regulates the expression of HLA class I antigens and of ICAM-1, resulting in improved recognition of cancer cells by gp100-specific CTL.
in vivo	Guadecitabine (SGI-110) is as effective as 5-Aza-CdR, but is better tolerated in mice. This compound (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. It is effective by both i.p. and s.c. deliveries.

製品説明

Guadecitabine (SGI-110, S-110) は、その活性代謝物であるデシタビンが静脈内デシタビンよりも長い生体内曝露時間を有する次世代の低メチル化剤です。

in vitro

Guadecitabine (SGI-110) is a 5-aza-2′-deoxycytidine-containing demethylating dinucleotide that works via a mechanism similar to that of 5-aza-CdR after incorporation of its aza-moiety into DNA. However, it is well protected from deamination by cytidine deaminase. This compound (1 μM) induces a significant decrease in the level of methylation in both T24 and HCT116 cells and is able to induce robust p16 expression. It also causes depletion of extractable DNMT1 in cells at 1 μM concentration. Furthermore, it 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.

It shows immunomodulatory activity in vitro. At 1 μM, it 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. This compound also up-regulates the expression of HLA class I antigens and of ICAM-1, resulting in improved recognition of cancer cells by gp100-specific CTL.

in vivo

Guadecitabine (SGI-110) is as effective as 5-Aza-CdR, but is better tolerated in mice. This compound (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. It is effective by both i.p. and s.c. deliveries.

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 Guadecitabine (SGI-110).
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

https://pubmed.ncbi.nlm.nih.gov/17616700/
https://pubmed.ncbi.nlm.nih.gov/23138873/
https://pubmed.ncbi.nlm.nih.gov/20442312/

https://pubmed.ncbi.nlm.nih.gov/31060979/
https://pubmed.ncbi.nlm.nih.gov/35843958/

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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：

Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition [ J Exp Clin Cancer Res, 2025, 44(1):21]	PubMed: 39844304
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 inhibition promotes recruitment of myeloid-derived suppressor cells to the tumor microenvironment through induction of tumor cell-intrinsic interleukin-1 [ Cancer Letters, 2023, 215982]	PubMed: nan
DNA Methyltransferase 1 Targeting Using Guadecitabine Inhibits Prostate Cancer Growth by an Apoptosis-Independent Pathway [ Cancers, 2023, 2763]	PubMed: nan
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
DNA methylation subtypes guiding prognostic assessment and linking to responses the DNA methyltransferase inhibitor SGI-110 in urothelial carcinoma [ BMC Medicine, 2022, 222]	PubMed: 35843958.0
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

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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