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IOX2

CAS No. : 931398-72-0

MCE 站：IOX2

产品活性：IOX2 是一种特异性的脯氨酰羟化酶-2 (PHD2) 抑制剂，IC₅₀ 为 22 nM。

研究领域：Metabolic Enzyme/Protease

作用靶点：HIF/HIF Prolyl-Hydroxylase

In Vitro: IOX2 is at least 2-5000 fold selective, as judged by IC₅₀ values, for PHD2 over the KDMs and Factor Inhibiting HIF(FIH). IOX2 significantly upregulates the transcription of VEGF-A and BNIP3 in normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF) when grown under normoxia and hypoxia. IOX2 efficiently promotes HIF-1α stability, nuclear translocation, and target gene expression in keratinocytes and fibroblasts. In addition, IOX2 significantly upregulates biosynthesis and transcription of VEGF-A and BNIP3 in sulfur mustard (SM)-exposed NHEK and NHDF grown under hypoxia. These results suggest that application of IOX2 is useful for restoring of SM-affected HIF-1α stability and signaling activity in keratinocytes and fibroblasts.

In Vivo: To investigate the utility of IOX2 as in vivo functional probes, IOX2 is tested to upregulate HIF signaling in a whole organism, that is, transgenic zebrafish (Danio rerio). Because the expression of the PHD3 encoding gene is regulated by HIF in humans and zebrafish, PHD3 levels are a readout of HIF activity. A zebrafish hypoxia reporter line is generated expressing GFP with the phd3 promoter elements. Transgenic wild-type embryos at 3 days postfertilization treated with compounds (10 μM) for 2 days displayed clear increase in phd3:EGFP expression in the liver, relative to controls. Significant increases in GFP levels are observed with IOX2.

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