IOX2

製品コードS2919 バッチS291901

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	7 mg/mL (19.86 mM)
		Water	Insoluble
		Ethanol	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	IOX2 (JICL38) is a potent inhibitor of HIF-1α prolyl hydroxylase-2 (PHD2) with IC50 of 21 nM in a cell-free assay, >100-fold selectivity over JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH.
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). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. ^[1] 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. ^[2]

製品説明

IOX2 (JICL38) is a potent inhibitor of HIF-1α prolyl hydroxylase-2 (PHD2) with IC50 of 21 nM in a cell-free assay, >100-fold selectivity over JMJD2A, JMJD2C, JMJD2E, JMJD3, or the 2OG oxygenase FIH.

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). IOX2 is active in cells, inhibiting HIF-1α hydroxylation in RCC4 cells at 50 μM. ^[1] 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. ^[2]

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

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
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
RNA-seq analysis of PHD and VHL inhibitors reveals differences and similarities to the hypoxia response [ Wellcome Open Res, 2019, 04:17]	PubMed: 30801039

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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