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CEP-33779

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Chemical Structure| 1257704-57-6 同义名 : -
CAS号 : 1257704-57-6
货号 : A153169
分子式 : C24H26N6O2S
纯度 : 99%+
分子量 : 462.567
MDL号 : MFCD22683932
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 7 mg/mL(15.13 mM)，配合低频超声，并水浴加热至45℃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：

1% DMSO+30% PEG 300+1% Tween 80+water 30 mg/mL suspension

生物活性
靶点

  • JAK2

    JAK2, IC50:1.8 nM
描述 The JAK/STAT pathway forms a critical node affecting multiple signaling pathways in both the innate and adaptive immune responses. Janus kinase 2 (JAK2) belongs to the non-receptor tyrosine kinase family. JAK2 is widely distributed in the cytoplasm of a variety of somatic cells, involved in cell-cycle regulation, apoptosis, mitotic chromosome recombination, genetic instability, and heterochromatin changes, and other biological processes. CEP-33779 is a highly selective, small-molecule inhibitor of JAK2 with an IC50 of 1.8 nMDugan BJ, Gingrich DE, Mesaros EF, Milkiewicz KL, Curry MA, Zulli AL, Dobrzanski P, Serdikoff C, Jan M, Angeles TS, Albom MS, Mason JL, Aimone LD, Meyer SL, Huang Z, Wells-Knecht KJ, Ator MA, Ruggeri BA, Dorsey BD. A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779. J Med Chem. 2012 Jun 14;55(11):5243-54. doi: 10.1021/jm300248q. Epub 2012 May 18. PMID: 22594690.}https://pubmed.ncbi.nlm.nih.gov/22594690/. Administration of CEP-33779 in a therapeutic mode resulted in a reduction in colorectal tumor mass, decreased levels of proinflammatory cytokines, and inhibition of STAT3 and NF-κB activation. In addition, it caused histologic reductions in cancer grades, and a negative impact on the tumor microenvironment including reduced tumor cell proliferation and angiogenesis upon JAK2 inhibition. With advanced development, CEP-33779 can deplet the autoreactive plasma cells, treat lupus nephritis in mice, ablate disease in two different mouse models of rheumatoid arthritis and administration of CEP-33779 results in significant inhibition of tumor growth in an AOM/DSS-induced model of colorectal cancer[3]. In a vitro study, KBV20C cells were then stimulated for 72h with CEP-33779 ranging from 5-10 μM. The result showed that JAK2 inhibitor CEP-33779 increased sensitization of KBV20C cells to VIC-induced mitotic-arrest[4]. In a vivo study, using a mouse model of colitis-induced colorectal cancer, JAK2 inhibitor, CEP-33779 induced regression of established colorectal tumors, reduced angiogenesis, and reduced proliferation of tumor cells with an increasing doses of 10 mg/kg, 30 mg/kg, and 55 mg/kg[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
TF-1 cells Function assay 1 h Inhibition of JAK2 in human TF-1 cells using GM-CSF pretreated for 1 hr prior to GM-CSF addition measured after 5 hrs by FRET based GeneBLAzer assay, IC50=0.061 μM 22594690
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.81mL

2.16mL

1.08mL

21.62mL

4.32mL

2.16mL
参考文献

[1]Seavey MM, Lu LD, Stump KL, Wallace NH, Hockeimer W, O'Kane TM, Ruggeri BA, Dobrzanski P. Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer. Mol Cancer Ther. 2012 Apr;11(4):984-93. doi: 10.1158/1535-7163.MCT-11-0951. Epub 2012 Feb 14. PMID: 22334590.

[2]Cheon JH, Kim KS, Yadav DK, Kim M, Kim HS, Yoon S. The JAK2 inhibitors CEP-33779 and NVP-BSK805 have high P-gp inhibitory activity and sensitize drug-resistant cancer cells to vincristine. Biochem Biophys Res Commun. 2017 Sep 2;490(4):1176-1182. doi: 10.1016/j.bbrc.2017.06.178. Epub 2017 Jun 29. PMID: 28669723.