Enasidenib (AG-221)

製品コードS8205 バッチS820502

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₉H₁₇F₆N₇O
	分子量	473.38	CAS No.	1446502-11-9
Solubility (25°C)*	体外	DMSO	94 mg/mL (198.57 mM)
		Ethanol	94 mg/mL (198.57 mM)
		Water	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	Enasidenib (AG-221) is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzyme with IC50 of 12 nM.
in vitro	The compound has been demonstrated to reduce 2-HG levels by >90% and reverse histone and deoxyribonucleic acid (DNA) hypermethylation in vitro, and to induce differentiation in leukemia cell models^[2].
in vivo	AG-221 is able to potently reduce 2HG found in the bone marrow, plasma and urine of engrafted mice. Treatment also induced a dose dependent, statistically significant, survival benefit. A proliferative burst of the human specific CD45+ blast cells is followed by cellular differentiation as measured by the expression of CD11b, CD14 and CD15 and cell morphology after AG-221 treatment^[2]. AG-221 treatment also restores megakaryocyte-erythroid progenitor (MEP) differentiation that is suppressed by mutant IDH2 expression and reverses the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells. Clinical trials combining IDH2 inhibitors with other targeted AML therapies are warranted in order to increase therapeutic efficacy^[1].

製品説明

Enasidenib (AG-221) is a first-in-class, oral, potent, reversible, selective inhibitor of the IDH2 mutant enzyme with IC50 of 12 nM.

in vitro

The compound has been demonstrated to reduce 2-HG levels by >90% and reverse histone and deoxyribonucleic acid (DNA) hypermethylation in vitro, and to induce differentiation in leukemia cell models^[2].

in vivo

AG-221 is able to potently reduce 2HG found in the bone marrow, plasma and urine of engrafted mice. Treatment also induced a dose dependent, statistically significant, survival benefit. A proliferative burst of the human specific CD45+ blast cells is followed by cellular differentiation as measured by the expression of CD11b, CD14 and CD15 and cell morphology after AG-221 treatment^[2].

AG-221 treatment also restores megakaryocyte-erythroid progenitor (MEP) differentiation that is suppressed by mutant IDH2 expression and reverses the effects of mutant IDH2 on DNA methylation in mutant stem/progenitor cells. Clinical trials combining IDH2 inhibitors with other targeted AML therapies are warranted in order to increase therapeutic efficacy^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	OE19 cells
	濃度	5 μM
	反応時間	24 h
	実験の流れ	Cells were treated with different concentrations of Enasidenib.
動物実験	動物モデル	Murine models of IDH2-mutant leukemia
	投薬量	10 mg/kg or 100 mg/kg bid
	投与方法	--

参考

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：

Dysregulated Lipid Synthesis by Oncogenic IDH1 Mutation Is a Targetable Synthetic Lethal Vulnerability [ Cancer Discov, 2023, 13(2):496-515]	PubMed: 36355448
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709]	PubMed: 37726279
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709]	PubMed: 37726279
Succinate mediates inflammation-induced adrenocortical dysfunction [ Elife, 2023, 12e83064]	PubMed: 37449973
Phospholipid metabolic adaptation promotes survival of IDH2 mutant acute myeloid leukemia cells [ Cancer Sci, 2023, 10.1111/cas.15994]	PubMed: 37882467
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226]	PubMed: 36266272
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia [ Nat Commun, 2022, 13(1):6226]	PubMed: 36266272
Regulatory chromatin rewiring promotes metabolic switching during adaptation to oncogenic receptor tyrosine kinase inhibition [ Oncogene, 2022, 41(43):4808-4822]	PubMed: 36153371
Lysine acetylation restricts mutant IDH2 activity to optimize transformation in AML cells [ Mol Cell, 2021, S1097-2765(21)00507-4]	PubMed: 34289383
Mutant Idh2 cooperates with a NUP98-HOXD13 fusion to induce early immature thymocyte precursor ALL [ Cancer Res, 2021, canres.1027.2021]	PubMed: 34321240

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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