A potent inhibitor of JAK3
ZM 39923 is an inhibitor of JAK3 (IC50 = 79 nM) that less potently inhibits epidermal growth factor receptor, JAK1, and cyclin-dependent kinase 4 (IC50s = 2.4, 40, and 10 ?M, respectively).1 In the absence of the reducing agent dithiothreitol, ZM 39923 also inhibits human tissue transglutaminase 2 (TGM2) and the transglutaminase Factor XIIIa (IC50s= 10 and 25 nM, respectively).2 It breaks down in neutral buffer to form ZM 449829, which is also an inhibitor of JAK3, TGM2, and Factor XIIIa.1,2
1.Brown, G.R., Bamford, A.M., Bowyer, J., et al.Naphthyl ketones: A new class of Janus kinase 3 inhibitorsBioorg. Med. Chem. Lett.10(6)575-579(2000) 2.Lai, T.-S., Liu, Y., Tucker, T., et al.Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug librariesChem. Biol.15(9)969-978(2008)
Cell experiment: | PCI-37B (a metastatic SCCHN cell line expressing CCR7) cells are cultured in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum, penicillin, and streptomycin in an atmosphere of 5% CO2 and 95% air at 37°C. The ZM39923 inhibitor treatment at the dose determined using the Cell Counting Kit-8[3]. |
参考文献: [1]. Brown GR, et al. Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9. | |
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