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℃. The ZM39923 inhibitor treatment at the dose determined using the Cell Counting Kit-8[3]. |
产品描述 | ZM 39923 is a selective inhibitor of JAK1 and JAK3 with pIC50 value of 4.4 and 7.1, respectively [1] [2]. JAK (Janus kinase) is a member of intracellular, non-receptor tyrosine kinases family and plays a pivotal role in transducing cytokine-mediated signals via the JAK-STAT pathway. It has been shown that type I and type II cytokine receptor families rely on the JAK family to phosphorylate and activate downstream proteins involved in their signal transduction pathways. Considering the biological function of JAK, a veraity of JAK inhibitors have been developed and mainly used for screening blood system disease, tumor, rheumatoid arthritis and psoriasis treatment [2] [3]. ZM 39923 is a selective JAK1 and JAK3 inhibitor. When tested with RA cells, administration of ZM 39923 combined with 50 μg/ml curcumol suppressed CD4(+) T cell proliferation and induced apoptosis through inhibiting Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively [4]. In confluent ARPE-19 cells, pretreated with ZM 39923 followed acrolein treatment resulted in the reduction of cell viability and increased VEGF expression via mediating JAK3 and TGFβ2 [3]. It is reported that ZM 39923 has the inhibitory effect on TGM2 (which considered as a target for several disease treatment) with the IC50 value of 10 nM [5] and the same effect on EGFR [1]. References: [1]. Luo, C. and P. Laaja, Inhibitors of JAKs/STATs and the kinases: a possible new cluster of drugs. Drug Discov Today, 2004. 9(6): p. 268-75. [2]. Brown, G.R., et al., Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett, 2000. 10(6): p. 575-9. [3]. Vidro-Kotchan, E., et al., NBHA reduces acrolein-induced changes in ARPE-19 cells: possible involvement of TGFbeta. Curr Eye Res, 2011. 36(4): p. 370-8. [4]. Wang, H., et al., The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat cells, a model of CD4(+) T cells. Int Immunopharmacol, 2014. 21(2): p. 375-82. [5]. Lai, T.S., et al., Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem Biol, 2008. 15(9): p. 969-78. |