GI 254023X
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50值: 5.3 nM (ADAM10)
去整合素金属蛋白酶10(也称为ADAM10或CDw156或 CD156c)是在人体内经ADAM10基因编码的蛋白质.ADAM10 (EC#: 3.4.24.81)是一种脱落酶,对多肽水解反应具有广泛的特异性.由GSK合成的GI 254023X 对ADAM10的抑制作用是对ADAM17的100倍.GI 254023X可减少ECV-304转染子对分形素(fractilkine)的组成型切割[1].
体外实验:之前的研究报道,化合物GI254023X仅对ADAM10具有可比性的抑制效力,且以减少了超过100倍的效力阻滞TACE[2].
体内实验:为了检验GI254023X在体内抑制Hla介导的内皮屏障破坏能力,在小鼠皮下注射重组毒素,在3天周期内给小鼠腹腔内注射GI254023X,随后进行Miles试验.结果表明,尽管所有的实验动物都死于该致命挑战,GI254023X用药的小鼠在外表看起来没那么严重,且死亡时间有所延后[3].
临床试验:目前GI254023X处于临床前发展阶段,还没有进行临床试验.
参考文献:
[1] Koichi Yokota, and Shin-Ichiro Nishimura. MMP/ADAM inhibitors: therapeutic potential for psoriasis. Expert Opin. Ther. Patents. 2005;15:421-435
[2] Hundhausen C, Misztela D, Berkhout TA, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V, Kallen KJ, Rose-John S, Ludwig A. The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood. 2003;102(4):1186-95.
[3] Powers ME, Kim HK, Wang Y, Bubeck Wardenburg J. ADAM10 mediates vascular injury induced by Staphylococcus aureus α-hemolysin. J Infect Dis. 2012;206(3):352-6.
- 1.Gao Y, Yang F, et al. "β1,6 GlcNAc branches-modified protein tyrosine phosphatase Mu attenuates its tyrosine phosphatase activity and promotes glioma cell migration through PLCγ-PKC pathways." Biochem Biophys Res Commun. 2018 Oct 28;505(2):569-577. PMID:30274773
- 2.Feng L, Wang Y, et al. "ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice." J Cell Sci. 2016 Jun 1;129(11):2202-12. PMID:27084580
Physical Appearance | White solid |
Storage | Store at -20°C |
M.Wt | 391.5 |
Cas No. | 260264-93-5 |
Formula | C21H33N3O4 |
Solubility | ≥42.6 mg/mL in DMSO; ≥46.1 mg/mL in EtOH; insoluble in H2O |
Chemical Name | (2R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-[(1S)-1-[formyl(hydroxy)amino]ethyl]-5-phenylpentanamide |
SDF | Download SDF |
Canonical SMILES | CC(C(CCCC1=CC=CC=C1)C(=O)NC(C(=O)NC)C(C)(C)C)N(C=O)O |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |
细胞实验[1, 2]: | |
细胞系 |
Jurkat细胞,人肺动脉内皮细胞(HPAECs) |
溶解方法 |
该化合物在DMSO中的溶解度> 10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
反应条件 |
20 μM, 16-18h |
应用 |
在Jurkat细胞中,GI 254023X以浓度依赖性方式抑制细胞增殖和增加细胞凋亡。与对照组相比,GI 254023X以时间依赖性方式上调Notch1的表达,同时下调切割的Notch1的表达。GI254023X还降低MCL-1和Hes-1 mRNA转录物的水平。在人肺动脉内皮细胞(HPAECs)中,GI254023X抑制VE-钙粘蛋白的切割,并完全保护HPAEC免受Hla介导的屏障破坏。 |
动物实验[2]: | |
动物模型 |
注射无内毒素重组Hla的BALB/c小鼠 |
剂量 |
200 mg/kg/day, 在0.1M碳酸盐缓冲液中稀释,3天时间,腹膜内注射 |
应用 |
在注射无内毒素重组Hla的BALB/c小鼠中,GI254023X增强血管完整性,通过有限的染料外渗表现,表明GI254023X可以提供保护免受致死感染。小鼠用DMSO或GI254023X处理,然后用5×107 CFU金黄色葡萄球菌Newman感染。GI254023X治疗的小鼠外观较少病态,延长了死亡时间。 |
注意事项 |
请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。 |
References: [1]. Ma S1,2, Xu J1, Wang X1,2, et al. Effect of ADAM10 Inhibitor GI254023X on Proliferation and Apoptosis of Acute T-Lymphoblastic Leukemia Jurkat Cells In Vitro and Its Possible Mechanisms. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015 Aug;23(4):950-5. [2] Powers ME, Kim HK, Wang Y, Bubeck Wardenburg J.ADAM10 mediates vascular injury induced by Staphylococcus aureus α-hemolysin. J Infect Dis. 2012;206(3):352-6. |
质量控制和MSDS
- 批次: