PF-06726304

製品コードS8494 バッチS849401

化学情報

	Synonyms	PF-6726304	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₁Cl₂N₃O₃
	分子量	446.33	CAS No.	1616287-82-1
Solubility (25°C)*	体外	Ethanol	22 mg/mL (49.29 mM)
		DMSO	10 mg/mL (22.4 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	PF-06726304 is a selective EZH2 inhibitor with Ki values of 0.7 nM and 3 nM for WT EZH2 and Y641N respectively; also inhibits H3K27me3 with the IC50 value of 15 nM.
in vitro	PF-06726304 displays very potent EZH2 biochemical inhibition as well as good activity in the cell H3K27Me3 reduction and antiproliferation effect^[1].
in vivo	PF-06726304 displays robust in vivo antitumor growth activity and dose-dependent de-repression of EZH2 target genes. PF-06726304 displays good efficacy in a diffuse large B-cell lymphoma Karpas-422 tumor model and exhibited on-target pharmacodynamic effects in vivo^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Karpas-422 cell line
	濃度	--
	反応時間	72 h
	実験の流れ	Karpas-422 cells are plated in complete cell culture medium (100 μL/well) in a 96-well clear, V bottom polystyrene cell culture plate at a density of 2500 cells/well. The cells are then incubated for 2−3 h at 37 °C and 5% CO2. Compound dilution plates are prepared in 96-well clear, U-bottom polypropylene plates in 100% DMSO at 10 mM stock concentration in duplicate wells using an 11-point serial dilution (1:3 dilutions). Compounds are further diluted in growth medium, and 25 μL is added to each well of the cell plates. The highest compound concentration tested is 50 μM final, with a 0.5% final DMSO concentration. The plates are then incubated for 72 h at 37 °C and 5% CO2. At the end of the incubation period with compound, the plates are centrifuged at 2000 rpm for 5 min at room temperature, and the medium is removed. Then 100 μL of acid-extracted solution is added to each well. The plates are shaken for 50 min at 4 °C to lyse the cells, and then 38 μL of neutralization buffer is added. The plates are then frozen at −80 °C. The next day, the plates are shaken at room temperature to thaw. Cell lysates (50 μL/well) are then transferred to ELISA plates. The plates are covered and incubated for 2.5 h at room temperature with constant slow-speed shaking. After incubation, the plates are washed seven times (300 μL/well) with 1× wash buffer. Then 100 μL of biotinylated trimethylhistone H3K27 detection antibody is added to each well and incubated for 2 h at room temperature with constant slow-speed shaking. After incubation, the plates are washed as described above. Horseradish peroxidase-linked antibody (100 μL) is added to each well and incubated for 60 min at room temperature with constant slow-speed shaking. After incubation, the plates are washed. Finally, 100 μL of TMB substrate reagent is added to each well and incubated for 5 min at room temperature in the dark with slow shaking, after which 100 μL of stop solution is added to stop the reaction.
動物実験	動物モデル	Female Scid beige mice
	投薬量	30, 100, 300 mg/kg
	投与方法	oral

参考

[1] Pei-Pei Kung, et al. J Med Chem. 2016, 59 (18): 8306-8325.

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：

Cathepsin-facilitated invasion of BMI1-high hepatocellular carcinoma cells drives bile duct tumor thrombi formation [ Nat Commun, 2023, 10.1038/s41467-023-42930-y]	PubMed: 37923799
Quantitative control of noise in mammalian gene expression by dynamic histone regulation [ Elife, 2021, 10e65654]	PubMed: 34379055

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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