EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #100-0518_C
抑制蛋白精氨酸脱亚胺酶（PAD）
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总览
Cl-Amidine是一种蛋白精氨酸脱亚胺酶（PAD）抑制剂，通过修饰酶的活性位点可不可逆地使4种PAD亚型失活(kinact/Ki = 37000 /PAD1、1200 /PAD2、2000 /PAD3和13000 /PAD4 M-1min-1；Knuckley et al.；Luo et al.；Slack et al.)。本品以分子的盐酸盐形式供应。
免疫学
·抑制中性粒细胞胞外陷阱的形成（Knight et al.）。
·防止中性粒细胞组蛋白H3的超细化（Knight et al.）。
癌症研究
·显示对人类白血病（IC50 = 0.25 μM）、乳腺癌（IC50 = 0.05 μM）和结肠癌（IC50 = 1 μM）癌细胞系（Slack et al.）的细胞毒性作用。
别名
不适用
细胞类型
癌细胞及细胞系，粒细胞及其亚群
研究领域
癌症，免疫
CAS 编号
1373232-26-8
化学式
• C14H19ClN4O2
• HCl
分子量
347.2 g/mol
纯度
≥ 95 %
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
相关材料与文献
技术资料 (4)
文献 (5)
Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization.
Biochemistry 2006 oct
Abstract
Protein arginine deiminase 4 (PAD4) is a transcriptional coregulator that catalyzes the calcium-dependent conversion of specific arginine residues in proteins to citrulline. Recently,we reported the synthesis and characterization of F-amidine,a potent and bioavailable irreversible inactivator of PAD4. Herein,we report our efforts to identify the steric and leaving group requirements for F-amidine-induced PAD4 inactivation,the structure of the PAD4-F-amidine x calcium complex,and in vivo studies with N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine),a PAD4 inactivator with enhanced potency. The PAD4 inactivators described herein will be useful pharmacological probes in characterizing the incompletely defined physiological role(s) of this enzyme. In addition,they represent potential lead compounds for the treatment of rheumatoid arthritis because a growing body of evidence supports a role for PAD4 in the onset and progression of this chronic autoimmune disorder.
Substrate specificity and kinetic studies of PADs 1, 3, and 4 identify potent and selective inhibitors of protein arginine deiminase 3.
Biochemistry 2010 jun
Abstract
Protein citrullination has been shown to regulate numerous physiological pathways (e.g.,the innate immune response and gene transcription) and is,when dysregulated,known to be associated with numerous human diseases,including cancer,rheumatoid arthritis,and multiple sclerosis. This modification,also termed deimination,is catalyzed by a group of enzymes called the protein arginine deiminases (PADs). In mammals,there are five PAD family members (i.e.,PADs 1,2,3,4,and 6) that exhibit tissue-specific expression patterns and vary in their subcellular localization. The kinetic characterization of PAD4 was recently reported,and these efforts guided the development of the two most potent PAD4 inhibitors (i.e.,F- and Cl-amidine) known to date. In addition to being potent PAD4 inhibitors,we show here that Cl-amidine also exhibits a strong inhibitory effect against PADs 1 and 3,thus indicating its utility as a pan PAD inhibitor. Given the increasing number of diseases in which dysregulated PAD activity has been implicated,the development of PAD-selective inhibitors is of paramount importance. To aid that goal,we characterized the catalytic mechanism and substrate specificity of PADs 1 and 3. Herein,we report the results of these studies,which suggest that,like PAD4,PADs 1 and 3 employ a reverse protonation mechanism. Additionally,the substrate specificity studies provided critical information that aided the identification of PAD3-selective inhibitors. These compounds,denoted F4- and Cl4-amidine,are the most potent PAD3 inhibitors ever described.
Protein arginine deiminase 4: a target for an epigenetic cancer therapy.
Cellular and molecular life sciences : CMLS 2011 feb
Abstract
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted the important role that epigenetics plays in human diseases,and suggested that the factors controlling gene expression are novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine,two potent PAD4 inhibitors,display micromolar cytotoxic effects towards several cancerous cell lines (HL-60,MCF7 and HT-29); no effect was observed in noncancerous lines (NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally,these compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together,these findings suggest PAD4 inhibition as a novel epigenetic approach for the treatment of cancer,and suggest that F- and Cl-amidine are candidate therapeutic agents for this disease.
更多信息
| Molecular Weight | 347.2 g/mol |
|---|---|
| Alternative Names | Not applicable |
| Cas Number | 1373232-26-8 |
| Chemical Formula | C14H19ClN4O2 • HCl |
| 纯度 | ≥ 95 % |
质量保证:
产品仅供研究使用，不用于针对人或动物的诊断或治疗。
产品仅供研究使用，不用于针对人或动物的诊断或治疗。
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