IOX2

製品コードS2919 バッチS291902

印刷

化学情報

Synonyms

JICL38

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₉H₁₆N₂O₅

分子量

352.34

CAS No.

931398-72-0

Solubility (25°C)*

体外

DMSO

10 mg/mL (28.38 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 30%PEG300 2 65%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	2.000mg/ml (5.68mM)	Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; then continue to add 650 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

* <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	IOX2（JICL38）は、細胞フリーアッセイにおいて21 nMのIC50を示すHIF-1αプロリルヒドロキシラーゼ-2（PHD2）の強力な阻害剤であり、JMJD2A、JMJD2C、JMJD2E、JMJD3、または2OGオキシゲナーゼFIHに対して100倍以上の選択性を示します。
in vitro	IOX2 potently inhibits PHD2 (IC50 of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). This compound is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. Hypoxia Inducible Factor (HIF) is regulated by the hydroxylation of prolyl residues in oxygen-dependent degradation domains in the HIF-1α subunit, which mark it for degradation by the proteosome. 1,2 HIF prolyl hydroxylation is catalyzed by prolyl hydroxylase domain enzymes (PHD1, 2, and 3), members of the Fe(II) and 2-oxoglutarate (2OG) oxygenase family. They require dioxygen as a cosubstrate, thus acting as the hypoxia-sensing component of the HIF system. The activity of PHD is suppressed by hypoxia, increasing both the abundance and activity of the HIF transcriptional complex.

製品説明

IOX2（JICL38）は、細胞フリーアッセイにおいて21 nMのIC50を示すHIF-1αプロリルヒドロキシラーゼ-2（PHD2）の強力な阻害剤であり、JMJD2A、JMJD2C、JMJD2E、JMJD3、または2OGオキシゲナーゼFIHに対して100倍以上の選択性を示します。

in vitro

IOX2 potently inhibits PHD2 (IC50 of 21 nM) with over 100-fold selectivity compared to inhibition of JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH (IC50s <100 μM). This compound is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. Hypoxia Inducible Factor (HIF) is regulated by the hydroxylation of prolyl residues in oxygen-dependent degradation domains in the HIF-1α subunit, which mark it for degradation by the proteosome. 1,2 HIF prolyl hydroxylation is catalyzed by prolyl hydroxylase domain enzymes (PHD1, 2, and 3), members of the Fe(II) and 2-oxoglutarate (2OG) oxygenase family. They require dioxygen as a cosubstrate, thus acting as the hypoxia-sensing component of the HIF system. The activity of PHD is suppressed by hypoxia, increasing both the abundance and activity of the HIF transcriptional complex.

プロトコル(参考用のみ)

キナーゼアッセイ	Alpha Screen Assay
キナーゼアッセイ	All reagents are 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 are run in 10 μM volumes in low-volume 384-well plates at RT. The reaction consists of enzyme (0.5-25nM), biotinylated substrate peptide (30-1000 nM), Fe(II) (1-10 μM), Ascorbate (100 μM), 2OG (5-40 μM) and run at RT. EDTA is used to quench the reaction (5 μM) and AlphaScreen donor (Streptavidin-conjugated) and acceptor (ProteinA-conjugated) beads preincubated with peptide product antibodies are added (5 μM). Plates are foil-sealed to protect from light, incubated at room temperature for 60 minutes 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 is 20 μM/mL. IC50 values are calculated in Prism 5 after normalization against corresponding DMSO c

参考

https://pubmed.ncbi.nlm.nih.gov/20666436/
https://pubmed.ncbi.nlm.nih.gov/21335549/

カスタマーフィードバック

: Data from [Data independently produced by , , Arch Toxicol, 2016, 90(5):1141-50]

: Data from [Data independently produced by , , Arch Toxicol, 2015, 10.1007/s00204-015-1549-y ]

: Data from [Data independently produced by , , Thromb Haemost, 2017, 117(10):1875-1886]

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：

Inhibition of CD38 enzymatic activity enhances CAR-T cell immune-therapeutic efficacy by repressing glycolytic metabolism [ Cell Rep Med, 2024, 5(2):101400]	PubMed: 38307031
Hypoxia Regulates Brown Adipocyte Differentiation and Stimulates miR-210 by HIF-1α [ Int J Mol Sci, 2024, 26(1)117]	PubMed: 39795975
iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation [ Oncogene, 2022, 41(13):1944-1958]	PubMed: 35169254
Pseudohypoxic HIF pathway activation dysregulates collagen structure-function in human lung fibrosis [ Elife, 2022, 11e69348]	PubMed: 35188460
Upregulation of HIF-1α contributes to complement activation in transplantation-associated thrombotic microangiopathy [ Br J Haematol, 2022, 10.1111/bjh.18377]	PubMed: 35864790
Von Hippel-Lindau (VHL) small molecule inhibitor binding increases stability and intracellular levels of VHL protein [ J Biol Chem, 2021, S0021-9258(21)00710-9]	PubMed: 34174286
ITRAQ-based quantitative proteomic analysis of MG63 in response to HIF-1α inducers. [ J Proteomics, 2020, 211:103558]	PubMed: 31655150
Metabolic Rewiring in Response to Biguanides Is Mediated by mROS/HIF-1a in Malignant Lymphocytes. [ Cell Rep, 2019, 29(10):3009-3018]	PubMed: 31801069
Propofol Alleviates Apoptosis Induced by Chronic High Glucose Exposure via Regulation of HIF-1α in H9c2 Cells [ Oxid Med Cell Longev, 2019, 2019:4824035]	PubMed: 31093315
EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells. [ Biochem Biophys Res Commun, 2019, 10.1016/j.bbrc.2019.07.039]	PubMed: 31331645

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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