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IOX2(Glycine)

Catalog No.
A4189
HIF-1α脯氨酰羟化酶-2(PHD2)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 850.00
现货
10mg
¥ 900.00
现货
50mg
¥ 3,500.00
现货

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Background

IOX2 is a potent and selective inhibitor of HIF-1α prolyl hydroxylase-2 (PHD2) with an IC50 of 21 nM for PHD2/ELGN-1 in a cell-free assay, IOX2 has shown >100-fold selectivity over JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH [1].

PHDs consist three isoforms, named PHD1, PHD2 and PHD3. PHDs are dioxygenases that utilize oxygen as co-substrate providing the molecular basis for the oxygen-sensing function of these enzymes. It has been reported that PHDs are strikingly sensitive to graded levels of hypoxia, mirroring the progressive increases in HIF-1α protein and DNA binding activity that are observed when cells are exposed to gradual hypoxia [2]. In RCC4 cells, IOX2 inhibited HIF-1α hydroxylation at 50 μM [1].

References:
[1] Murray J K, Balan C, Allgeier A M, et al.  Dipeptidyl-quinolone derivatives inhibit hypoxia inducible factor-1α prolyl hydroxylases-1,-2, and-3 with altered selectivity[J]. Journal of combinatorial chemistry, 2010, 12(5): 676-686.
[2] Berra E, Benizri E, Ginouvès A, et al.  HIF prolyl‐hydroxylase 2 is the key oxygen sensor setting low steady‐state levels of HIF‐1α in normoxia[J]. The EMBO journal, 2003, 22(16): 4082-4090.

文献引用

1.LUKE ERBER. "Functional Proteomics Analysis To Discover And Characterize Oxygen-Dependent Cellular Pathways." UNIVERSITY OF MINNESOTA. 2019.
2.Zhou T, Erber L, et al. "Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells." Oncotarget. 2016 Nov 29;7(48):79154-79169. PMID:27764789

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt352.34
Cas No.931398-72-0
FormulaC19H16N2O5
Solubility≥17.6 mg/mL in DMSO,insoluble in EtOH,insoluble in H2O
Chemical Name2-[(1-benzyl-4-hydroxy-2-oxoquinoline-3-carbonyl)amino]acetic acid
SDFDownload SDF
Canonical SMILESC1=CC=C(C=C1)CN2C3=CC=CC=C3C(=C(C2=O)C(=O)NCC(=O)O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

Alpha筛选实验

使用50 mM HEPES,0.1 % BSA,pH 7.5溶液稀释试剂,加入0.01 % Tween20,在室温下使其平衡,然后将其加入到实验板中。在室温下,使用低容量384孔板进行催化转换实验。反应体系包含0.5 ~ 25 nM酶,30 ~ 1000 nM生物素化的底物肽,1 ~ 10 μM Fe(II),100 μM抗坏血酸盐以及5 ~ 40 μM 2OG,在室温下进行反应。使用EDTA终止反应 (5 μM)。将AlphaScreen供体(链霉亲和素共轭)受体(蛋白A共轭)珠先与多肽产物抗体孵育,再将其加入上述反应体系 (5 μM) 中。使用箔密封实验板,使其避光,在室温下温育60分钟。在PHERAstar FS酶标仪上,以680 nm激发波长/570 nm发射波长为参数,对样品进行读数。在20 μM反应体系中,珠粒的最终浓度为20 μM/mL。使用Prism 5计算IC50值。

细胞实验 [1]:

细胞系

RCC4细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

50 μM

实验结果

在RCC4细胞中,IOX2 (50 μM) 抑制HIF-1α羟基化。

References:

[1]. Murray JK1, Balan C, Allgeier AM et al. Dipeptidyl-quinolone derivatives inhibit hypoxia inducible factor-1α prolyl hydroxylases-1, -2, and -3 with altered selectivity. J Comb Chem. 2010 Sep 13;12(5):676-86.

生物活性

Description IOX2 is a potent inhibitor of HIF-1α prolyl hydroxylase-2 (PHD2) with IC50 of 21 nM.
Targets PHD2          
IC50 21 nM          

质量控制

化学结构

IOX2

相关生物数据

IOX2

相关生物数据

IOX2