IOX2(Glycine)
目录号 : GC13018A selective PHD2 inhibitor
Cas No.:931398-72-0
Sample solution is provided at 25 µL, 10mM.
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.
Kinase experiment [1]: | |
Alpha screen assay |
All reagents were diluted in 50 mM HEPES, 0.1 % BSA, pH 7.5 supplemented with 0.01 % Tween20 and allowed to equilibrate to room temperature prior to addition to plates. Catalytic turnover assays were run in 10 μM volumes in low-volume 384-well plates at RT. The reaction consisted of enzyme (0.5 ~ 25 nM), biotinylated substrate peptide (30 ~ 1000 nM), Fe(II) (1 ~ 10 μM), Ascorbate (100 μM), 2OG (5 ~ 40 μM) and run at RT. EDTA was used to quench the reaction (5 μM) and AlphaScreen donor (Streptavidin-conjugated) and acceptor (ProteinA-conjugated) beads preincubated with peptide product antibodies were added (5 μM). Plates were foil-sealed to protect from light, incubated at room temperature for 60 mins and read on a PHERAstar FS plate reader using an AlphaScreen 680 excitation/570 emission filter set. The final bead concentration in 20 μM reaction was 20 μM/mL. IC50 values were calculated in Prism 5. |
Cell experiment [1]: | |
Cell lines |
RCC4 cells |
Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20 °C for several months. |
Reaction Conditions |
50 μM |
Applications |
In RCC4 cells, IOX2 inhibited HIF-1α hydroxylation at 50 μM. |
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. |
Cas No. | 931398-72-0 | SDF | |
化学名 | 2-[(1-benzyl-4-hydroxy-2-oxoquinoline-3-carbonyl)amino]acetic acid | ||
Canonical SMILES | C1=CC=C(C=C1)CN2C3=CC=CC=C3C(=C(C2=O)C(=O)NCC(=O)O)O | ||
分子式 | C19H16N2O5 | 分子量 | 352.34 |
溶解度 | ≥ 17.6 mg/mL in DMSO | 储存条件 | Store at -20°C |
General tips | 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。 储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。 为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。 |
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Shipping Condition | 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。 |
制备储备液 | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.8382 mL | 14.1908 mL | 28.3817 mL |
5 mM | 0.5676 mL | 2.8382 mL | 5.6763 mL |
10 mM | 0.2838 mL | 1.4191 mL | 2.8382 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
给药剂量 | mg/kg | 动物平均体重 | g | 每只动物给药体积 | ul | 动物数量 | 只 | |||
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方) | ||||||||||
% DMSO % % Tween 80 % saline | ||||||||||
计算重置 |
计算结果:
工作液浓度: mg/ml;
DMSO母液配制方法: mg 药物溶于 μL DMSO溶液(母液浓度 mg/mL,
体内配方配制方法:取 μL DMSO母液,加入 μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入 μL saline,混匀澄清。
1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet