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AZ191

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Chemical Structure| 1594092-37-1 同义名 : -
CAS号 : 1594092-37-1
货号 : A404720
分子式 : C24H27N7O
纯度 : 98%
分子量 : 429.517
MDL号 : MFCD28015098
存储条件：

粉末 Keep in dark place,Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(69.85 mM)，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

  • DYRK1

    DYRK1A, IC50:88 nM

    DYRK1B, IC50:17 nM
描述 The DYRKs (dual-specificity tyrosine phosphorylation-regulated kinases) are an evolutionarily conserved family of protein kinases that are found within the CMGC group[3].DYRKs contain a characteristic tyrosine-X-tyrosine (Y-X-Y) residue motif in their activation loop. Phosphorylation of the second tyrosine residue is critical for kinase activity[4]. AZ191 is a potent inhibitor that selectively inhibits DYRK1B with IC50 of 17 nM. Using in vitro kinase assays, phospho-specific immunoblot analysis and MS in conjunction with AZ191, DYRK1B phosphorylates CCND1 at Thr(286), not Thr(288), in vitro and in cells. In HEK (human embryonic kidney)-293 and PANC-1 cells (which exhibit DYRK1B amplification) DYRK1B drives Thr(286) phosphorylation and proteasome-dependent turnover of CCND1 and this is abolished by AZ191 or DYRK1B RNAi.[5]. AZ191 inhibited liposarcoma cell growth, decreased cell motility, and induced apoptosis. Moreover, combined AZ191 with doxorubicin demonstrated an increased anti-cancer effect on liposarcoma cells[6]. Mean inhibitory concentrations (EC50) of 0.98 ± 0.08 μM/SC84227, 0.60 ± 0.02 μM/SC97202, 6.26 ± 1.64 μM/SC97208, 0.71 ± 0.019 μM/Harmine and 0.63 ± 0.23 μM/AZ-191 were determined with human cytomegalovirus strain AD169-GFP for the infection of primary human fibroblasts[7].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.64mL

2.33mL

1.16mL

23.28mL

4.66mL

2.33mL
参考文献

[1]Li Z, Jiang K, et al. Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells. Cancer Lett. 2016 Jan 28;370(2):332-44.

[2]Ashford AL, Oxley D, et al. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014 Jan 1;457(1):43-56.

[3]Becker, W. and Joost, H. G. Structural and functional characteristics of Dyrk, a novel subfamily of protein kinases with dual specificity. Prog. Nucleic Acid Res. Mol. Biol. 1999. 62, 1–17.

[4]Himpel, S.,et al. Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A. Biochem. 2001. 359, 497–505.

[5]Anne L Ashford,et al. A novel DYRK1B inhibitor AZ191 demonstrates that DYRK1B acts independently of GSK3β to phosphorylate cyclin D1 at Thr(286), not Thr(288). Biochem J. 2014. 457(1), 43-56.

[6]Hua Chen,et al. Targeting DYRK1B suppresses the proliferation and migration of liposarcoma cells. Oncotarget. 2017. 9(17),13154-13166.

[7]Corina Hutterer,et al. Inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (DYRK) exert a strong anti-herpesviral activity. Antiviral Res. 2017.143, 113-121.