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Chemical Structure| 856243-80-6 同义名 : Wp1130
CAS号 : 856243-80-6
货号 : A535148
分子式 : C19H18BrN3O
纯度 : 98+%
分子量 : 384.27
MDL号 : MFCD18839228
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(273.25 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Bcr-Abl

    Bcr-Abl, IC50:1.8 μM

  • DUB
描述 WP1130 is a partly selective DUB inhibitor, directly inhibiting DUB activity of USP9x, USP5, USP14, and UCH37, which are known to regulate survival protein stability and 26S proteasome function. WP1130 at 5μM induced rapid accumulation of polyubiquitinated (K48/K63-linked) proteins into juxtanuclear aggresomes, without affecting 20S proteasome activity. WP1130-mediated inhibition of tumor-activated DUBs resulted in downregulation of antiapoptotic and upregulation of proapoptotic proteins, such as MCL-1 and p53, in BV173 cells treated by 5μM WP1130 for 4h[3]. WP1130 at 5μM specifically and rapidly down-regulatef both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells, not requiring the participation of the proteasomal pathway. And this loss of Bcr/Abl protein correlated with the onset of apoptosis and reduced phosphorylation of Bcr/Abl substrates, including p-Stat5 and p-Hck. It was more effective in reducing leukemic versus normal hematopoietic colony formation and strongly inhibited colony formation of cells derived from patients with T315I mutant Bcr/Abl–expressing CML in blast crisis. WP1130 suppressed the growth of K562 heterotransplanted tumors of mice treated with WP1130 at 30mg/kg, i.p., every other day for 9 days[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human A375 cells Cytotoxicity assay 72 h Cytotoxicity against human A375 cells after 72 hrs by MTT assay, IC50=1.7 μM 24457091
human K562 cells Cytotoxicity assay 72 h Cytotoxicity against human K562 cells after 72 hrs by MTT assay, IC50=2.4 μM 24457091
human Mino cells Cytotoxicity assay 72 h Cytotoxicity against human Mino cells after 72 hrs by MTT assay, IC50=0.8 μM 24457091
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.60mL

0.52mL

0.26mL

13.01mL

2.60mL

1.30mL

26.02mL

5.20mL

2.60mL
参考文献

[1]Kapuria V, Peterson LF, et al. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010 Nov 15;70(22):9265-76.

[2]Bartholomeusz GA, Talpaz M, et al. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood. 2007 Apr 15;109(8):3470-8. Epub 2007 Jan 3.

[3]Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res. 2010 Nov 15;70(22):9265-76. doi: 10.1158/0008-5472.CAN-10-1530. Epub 2010 Nov 2. PMID: 21045142.

[4]Bartholomeusz GA, Talpaz M, Kapuria V, Kong LY, Wang S, Estrov Z, Priebe W, Wu J, Donato NJ. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood. 2007 Apr 15;109(8):3470-8. doi: 10.1182/blood-2006-02-005579. Epub 2007 Jan 3. PMID: 17202319; PMCID: PMC1852235.