YZ129
目录号 : GC66059YZ129 是 HSP90-磷酸酶-NFAT 通路的抑制剂,可抗胶质母细胞瘤,直接与 热休克蛋白 (HSP90) 结合,对NFAT核易位的 IC50 值为820 nM。YZ129 在 G2/M 期诱导GBM细胞周期阻滞,促进细胞凋亡,抑制肿瘤细胞增值和迁移。
Cas No.:1643120-60-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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YZ129 is an inhibitor of the HSP90-calcineurin-NFAT pathway against glioblastoma, directly binding to heat shock protein 90 (HSP90) with an IC50 of 820 nM on NFAT nuclear translocation. YZ129-induced GBM cell-cycle arrest at the G2/M phase promotes apoptosis and inhibited tumor cell proliferation and migration[1].
Cas No. | 1643120-60-8 | SDF | Download SDF |
分子式 | C19H12N2O2 | 分子量 | 300.31 |
溶解度 | DMSO : 5.6 mg/mL (18.65 mM; ultrasonic and warming and heat to 80°C) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.3299 mL | 16.6495 mL | 33.2989 mL |
5 mM | 0.666 mL | 3.3299 mL | 6.6598 mL |
10 mM | 0.333 mL | 1.6649 mL | 3.3299 mL |
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% DMSO % % Tween 80 % saline | ||||||||||
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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Discovery of Small-Molecule Inhibitors of the HSP90-Calcineurin-NFAT Pathway against Glioblastoma
Cell Chem Biol 2019 Mar 21;26(3):352-365.e7.PMID:30639261DOI:PMC6430684
Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the first-line treatment for GBM, they often cause chemoresistance and remain ineffective with recurrent GBM. Alternative therapeutics against GBM are urgently needed in the clinic. We report herein the discovery of a class of inhibitors (YZ129 and its derivatives) of the calcineurin-NFAT pathway that exhibited potent anti-tumor activity against GBM. YZ129-induced GBM cell-cycle arrest at the G2/M phase promoted apoptosis and inhibited tumor cell proliferation and migration. At the molecular level, YZ129 directly engaged HSP90 to antagonize its chaperoning effect on calcineurin to abrogate NFAT nuclear translocation, and also suppressed other proto-oncogenic pathways including hypoxia, glycolysis, and the PI3K/AKT/mTOR signaling axis. Our data highlight the potential for targeting the cancer-promoting HSP90 chaperone network to treat GBM.