Pinometostat (EPZ5676)

製品コードS7062 バッチS706207

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	C₃₀H₄₂N₈O₃
	分子量	562.71	CAS No.	1380288-87-8
Solubility (25°C)*	体外	DMSO	100 mg/mL warmed with 50ºC water bath (177.71 mM)
		Ethanol	100 mg/mL warmed with 50ºC water bath (177.71 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	Pinometostat (EPZ5676) is an S-adenosyl methionine (SAM) competitive inhibitor of protein methyltransferase DOT1L with K_i of 80 pM in a cell-free assay, demonstrating >37,000-fold selectivity against all other PMTs tested, inhibits H3K79 methylation in tumor. Phase 1.
in vitro	EPZ-5676 reduces H3K79 dimethylation with a cellular IC50 of 2.6 nM in MV4-11 cells. EPZ-5676 treatment results in concentration- and time-dependent reduction of H3K79 methylation without effect on the methylation status of other histone sites, which leads to inhibition of key MLL target genes and selective, apoptotic cell killing in MLL-rearranged leukemia cells. EPZ-5676 inhibits proliferation of MLL-AF4 rearranged cell line MV4-11 with an IC50 of 9 nM.
in vivo	EPZ-5676 continuously intravenous infusion for 21 days to xenograft model of MLL-rearranged leukemia, leads to dose-dependent anti-tumor activity. At the highest dose of 70.5 mg/kg/day, complete tumor regressions are achieved with no regrowth for up to 32 days after the cessation of treatment. No significant weight loss or obvious toxicity is observed in rats treated with EPZ-5676 during efficacy study.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MV4-11 cells
	濃度	0.003 uM
	反応時間	4 days
	実験の流れ	Cells were treated with various concentrations of EPZ-5676.
動物実験	動物モデル	NCr nu/nu mouse
	投薬量	20 mg/kg
	投与方法	i.p.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Haematologica, 2018, 103(7):1110-1123]

: Data from [Data independently produced by , , Theranostics, 2018, 8(16):4359-4371]

: Data from [Data independently produced by , , Cell Rep, 2014, 9(3): 1163-70 ]

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：

Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia [ Exp Hematol Oncol, 2023, 12(1):81]	PubMed: 37740239
DOT1L activity affects neural stem cell division mode and reduces differentiation and ASNS expression [ EMBO Rep, 2023, e56233.]	PubMed: 37382163
H4K20me1 plays a dual role in transcriptional regulation of regeneration and axis patterning in Hydra [ Life Sci Alliance, 2023, 6(5)e202201619]	PubMed: 36944423
Modelling acquired resistance to DOT1L inhibition exhibits the adaptive potential of KMT2A-rearranged acute lymphoblastic leukemia [ Exp Hematol Oncol, 2023, 12(1):81]	PubMed: 37740239
Retrospective identification of intrinsic factors that mark pluripotency potential in rare somatic cells [ bioRxiv, 2023, 2023.02.10.527870]	PubMed: 36798299
Derivation of totipotent-like stem cells with blastocyst-like structure forming potential [ Cell Res, 2022, 10.1038/s41422-022-00668-0]	PubMed: 35508506
MOZ and Menin-MLL Complexes are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor [ Cancer Discov, 2022, candisc.0646.2021]	PubMed: 35499757
MLL::AF9 degradation induces rapid changes in transcriptional elongation and subsequent loss of an active chromatin landscape [ Mol Cell, 2022, 82(6):1140-1155.e11]	PubMed: 35245435
Generation of mitochondria-rich kidney organoids from expandable intermediate mesoderm progenitors reprogrammed from human urine cells under defined medium [ Cell Biosci, 2022, 12(1):174]	PubMed: 36243732
Inhibition of the cardiac fibroblast-enriched histone methyltransferase Dot1L prevents cardiac fibrosis and cardiac dysfunction [ Cell Biosci, 2022, 12(1):134]	PubMed: 35986422

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。