AZ3146

"目录号: HY-14710

Cell Cycle/DNA DamageCytoskeleton-

AZ3146 是一种有效的选择性的Mps1抑制剂，作用于 Mps1Cat，IC50为 35 nM。

Mps1

相关产品

Mps1-IN-1-CFI-402257-BAY 1161909-BAY1217389-MPI-0479605-NMS-P715-Mps1-IN-2-Mps1-IN-3-

生物活性

Description

AZ3146 is a reasonably potent and selectiveMps1inhibitor withIC50of 35 nM for Mps1Cat.

IC50& Target

IC50: 35 nM (Mps1)[1]

In Vitro

In in vitro kinase assays, AZ3146 inhibits human Mps1Catwith IC50of ~35 nM. AZ3146 also efficiently inhibits autophosphorylation of full-length Mps1 immunoprecipitated from human cells[1]. TTK specific kinase inhibitor AZ3146 can decrease HCC cell growth. In vitro cell cytotoxicity assays are performed on SMMC-7721 and BEL-7404 cells. IC50s are calculated as being 7.13 μM (BEL-7404) and 28.62 μM (SMMC-7721). Both cells are further treated under the concentration of IC50 for 4 days. Significant inhibitions of cell proliferation are observed[2]. HCT116 cells are cultured for 10 days in 0.8 μM (the GI50) of AZ3146 , then 2 μM AZ3146 for 3 weeks. Sixteen clones are isolated and cell lines generated, named AzR1-16, all of which are resistant to AZ3146-induced cell death in cell viability assays; AzR3 and 4 have a GI50of approximately 3 μM (4-fold resistance), while the remaining clones have a GI50of approximately 9 μM (11-fold resistance). When analyzing mitosis by time-lapse microscopy, while 2 μM AZ3146 causes the parental cell line to rapidly exited mitosis in 10 minutes[3].

References

[1].Hewitt L, et al. Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex. J Cell Biol. 2010 Jul 12;190(1):25-34.

[2].Liu X, et al. TTK activates Akt and promotes proliferation and migration of hepatocellular carcinoma cells. Oncotarget. 2015 Oct 27;6(33):34309-20.

[3].Gurden MD, et al. Naturally Occurring Mutations in the MPS1 Gene Predispose Cells to Kinase Inhibitor Drug Resistance. Cancer Res. 2015 Aug 15;75(16):3340-54.