用于缺氧诱导因子（HIF）脯氨酰羟化酶的选择性小分子探针。
Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases.
作者信息
Chowdhury Rasheduzzaman, Candela-Lena José Ignacio, Chan Mun Chiang, Greenald David Jeremy, Yeoh Kar Kheng, Tian Ya-Min, McDonough Michael A, Tumber Anthony, Rose Nathan R, Conejo-Garcia Ana, Demetriades Marina, Mathavan Sinnakaruppan, Kawamura Akane, Lee Myung Kyu, van Eeden Freek, Pugh Christopher W, Ratcliffe Peter J, Schofield Christopher J
机构信息
Department of Chemistry, Chemistry Research Laboratory, University of Oxford , Mansfield Road, Oxford, OX1 3TA, United Kingdom.
出版信息
ACS Chem Biol. 2013 Jul 19;8(7):1488-96. doi: 10.1021/cb400088q. Epub 2013 Jun 12.
The hypoxia inducible factor (HIF) system is central to the signaling of low oxygen (hypoxia) in animals. The levels of HIF-α isoforms are regulated in an oxygen-dependent manner by the activity of the HIF prolyl-hydroxylases (PHD or EGLN enzymes), which are Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. Here, we describe biochemical, crystallographic, cellular profiling, and animal studies on PHD inhibitors including selectivity studies using a representative set of human 2OG oxygenases. We identify suitable probe compounds for use in studies on the functional effects of PHD inhibition in cells and in animals.
缺氧诱导因子（HIF）系统是动物低氧（缺氧）信号传导的核心。HIF-α亚型的水平由HIF脯氨酰羟化酶（PHD或EGLN酶）的活性以氧依赖的方式调节，这些酶是依赖Fe（II）和2-氧代戊二酸（2OG）的加氧酶。在此，我们描述了关于PHD抑制剂的生化、晶体学、细胞分析和动物研究，包括使用一组具有代表性的人类2OG加氧酶进行的选择性研究。我们确定了适用于研究PHD抑制在细胞和动物中的功能效应的探针化合物。
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