UNC1999 - CAS:1431612-23-5 - CAS号查询_生物试剂_化学试剂_分析试剂

中文名称:	UNC1999 促销
英文名称:	UNC1999
别名:	N-((1,2-二氢-6-甲基-2-氧代-4-丙基-3-吡啶基)甲基)-1-(1-甲基乙基)-6-(6-(4-(1-甲基乙基)-1-哌嗪基)-3-吡啶基)-1H-吲唑-4-甲酰胺 UNC1999;N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-1-propan-2-yl-6-[6-(4-propan-2-ylpiperazin-1-yl)pyridin-3-yl]indazole-4-carboxamide;S7165;UNC-1999;1-Isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide
CAS No:	1431612-23-5	分子式:	C₃₃H₄₃N₇O₂	分子量:	569.74
CAS No:	1431612-23-5
分子式:	C₃₃H₄₃N₇O₂
分子量:	569.74
MDL:	MFCD26960958

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U10007 UNC1999 ≥98%（HPLC） (psaitong)

相关产品

包装规格：

5mg 25mg in glass bottle

溶解性：

溶于DMSO(15mg/ml)

产品描述：

基本信息

产品编号：U10007
产品名称：UNC1999
CAS:	1431612-23-5	储存条件	粉末	2-8℃	四年

分子式：	C33H43N7O2		溶于液体	-80℃	六个月
分子量：	569.74			-20℃	一个月
化学名：
Solubility (25°C)	体外	DMSO	100mg/mL (175.51mM)
		Ethanol	100mg/mL (175.51mM)
		Water	Insoluble
	体内（现配现用）
＜1mg/ml表示微溶或不溶。
普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。

制备储备液

浓度溶液体积质量	1mg	5mg	10mg
1mM	1.7552mL	8.7759mL	17.5519mL
5mM	0.3510mL	1.7552mL	3.5104mL
10mM	0.1755mL	0.8776mL	1.7552mL
50mM	0.0351mL	0.1755mL	0.3510mL

生物活性

产品描述	一种有效的SAM竞争性的选择性EZH2和EZH1抑制剂,可参考结构基因组学协会(SGC)关于此产品的介绍。
靶点/IC50	EZH2 (Cell-free assay)	EZH1 (Cell-free assay)
	2nM	45nM
体外研究	UNC1999,the first orally bioavailable inhibitor that has high in vitro potency for wild-type and mutant EZH2 as well as EZH1,a closely related H3K27 methyltransferase that shares 96% sequence identity with EZH2 in their respective catalytic domains.UNC1999 is highly selective for EZH2 and EZH1 over a broad range of epigenetic and non-epigenetic targets,competitive with the cofactor SAM,and non-competitive with the peptide substrate.UNC1999 has Ki values of 4,700nM,65nM,300nM,and 1,500nM for sigma1,sigma2,histamine H3,and NET,respectively.NC1999 selectively kills DB cells,a DLBCL cell line with the EZH2 Y641N mutation.UNC1999 displays a concentration- and time-dependent inhibition of DB cell proliferation (EC50=633±101nM (n=3)).
体内研究	A single intraperitoneal (IP) injection of UNC1999 at 15,50,or 150mg/kg achieved high Cmax (9,700-11,800nM) and exhibited dose linearity in male Swiss albino mice.Both the 150 and 50mg/kg IP doses resulted in the plasma concentrations of UNC1999 above its cellular IC50 over the entire 24h period while the 15mg/kg IP dose led to the plasma concentrations of UNC1999 above its cellular IC50 for approximately 12h.We next examined whether UNC1999 is orally bioavailable and are pleased to find that a single 50mg/kg oral dose of UNC1999 achieved high Cmax (4,700nM) and good exposure levels in male Swiss albino mice.The plasma concentrations of UNC1999 are maintained above its cellular IC50 for approximately 20h following this single oral dose.It is worth noting that all doses including the 150mg/kg IP dose are well tolerated by all test mice,and no adverse effects are observed.

推荐实验方法(仅供参考)

激酶实验：

L of the dilution is added to a 50μL reaction so that the final concentration of DMSO is 1% in all of reactions.All of the enzymatic reactions are conducted in duplicate at room temperature for 60 minutes (EZH2) and 180 minutes (EZH2 Y641N) in a 50μL mixture containing HMT assay buffer,S-adenoslymethionine,enzyme,and UNC1999.These 50μL reactions are carried out in wells of a HMT substrate pre-coated plate.After enzymatic reactions,the reaction mixtures are discarded and each of the wells is washed three times with TBST buffer,and slowly shaken with Blocking Buffer for 10 minutes.Wells are emptied, and 100μL of diluted 1°antibody is added.The plate is then slowly shaken for 60 minutes at room temperature.As before, the plate is emptied and washed three times,and shaken with Blocking Buffer for 10 minutes at room temperature.After discarding the Blocking Buffer,100μL of diluted 2°antibody is added.The plate is then slowly shaken for 30 minutes at room temperature.As before, the plate is emptied and washed three times,and shaken with Blocking Buffer for 10 minutes at room temperature.Blocking Buffer is discarded and a mixture of the HRP chemiluminescent substrates is freshly prepared.100μL of this mixture is added to each empty well. Immediately,the luminescence of the samples is measured in a BioTek SynergyTM 2 microplate reader.

细胞实验:

DB cells,a diffuse-large B-cell lymphoma cell line harboring the EZH2 Y641N mutation,are obtained from ATCC and cultured in RPMI 1640 supplemented with 10% fetal bovine serum,antibiotics,and various concentration of UNC1999 (0.1,0.2,0.3,0.4,0.5,1,2,3,and 5μM) or UNC2400 and DMSO control.The medium containing the test compound or control is refreshed every three days.The numbers of viable cells from at least three independent experiments are measured using TC20 automated cell counter system.Total histones are prepared from cell nuclei using an acidic extraction protocol.About 1 microgram of total histones is separated using 15% of SDS-PAGE,transferred to PVDF membranes,and probed with histone antibodies.Antibodies used in this study are those against EZH2,general H3, and H3K27me3.

动物实验:

Mice

Standard PK studies are conducted using male Swiss albino mice at Sai Life Sciences. Four doses (15,50,and 150mg/kg IP,and 50mg/kg PO) of UNC1999 are evaluated. Each study lasted 24h.Plasma concentrations of UNC1999 reported at each of the eight time points (0.08,0.25,0.5,1,2,4,8,and 24h post dosing) are the average values from 3 test animals.

保存条件：

2-8℃

UN码：

HazardClass：

危害声明：

安全说明：

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