CEP-33779 is a highly selective JAK2 inhibitor with IC50 value of 1.8 nM, with much less potency against JAK1 and TYK2 with >40- and >800-fold IC50 values.
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].
CEP-33779 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
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
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