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PHA-680632

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Chemical Structure| 398493-79-3 同义名 : -
CAS号 : 398493-79-3
货号 : A165443
分子式 : C28H35N7O2
纯度 : 99%+
分子量 : 501.623
MDL号 : MFCD16038900
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(59.81 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：

IP 2% DMSO+2% Tween80+40% PEG300+water 11 mg/mL clear

PO 0.5% CMC-Na 43 mg/mL suspension

生物活性
靶点

  • Aurora A

    Aurora A, IC50:27 nM

  • Aurora B

    Aurora B, IC50:135 nM

  • Aurora C

    Aurora C, IC50:120 nM
描述 Aurora proteins belong to a small family of serine/threonine kinases, including three members: Aurora A, Aurora B, and the less well characterized Aurora C, that regulate the structure and function of the cytoskeleton and chromosomes and the interactions between these two at the kinetochore. They also regulate signalling by the spindle-assembly checkpoint pathway and cytokinesis. Perturbation of Aurora kinase expression or function might lead to cancer[3]. PHA-680632 is a novel, highly selective Aurora kinase inhibitor, with three Aurora kinases with IC50s of 27, 135 and 120 nM for Aurora A, B, and C respectively, that inhibits the phosphorylation of Histone H3 in Ser10, which is mediated by Aurora B kinase. In a vitro study, C33A, HeLa, HCT116, HT29 cell lines were treated with PHA-680632 and incubated for 72 hours. It indicates that PHA-680632 is a efficient cell cycle inhibitor with IC50 values of 0.32 μM, 0.41 μM, 0.06 μM and 1.17 μM for C33A, HeLa, HCT116, HT29 cell lines respectively. In a vivo study, A2780 human ovarian carcinoma and HCT116 colon carcinoma cell lines were transplanted s.c. into athymic mice. In the A2780 human ovarian carcinoma model, the dose of 60 mg/kg i.v. b.i.d. for 5 days showed potent tumor inhibition, reaching 78% of TGI compared with the vehicle-treated controls. A more prolonged exposure to PHA-680632 was tested in the HCT116 colon carcinoma xenograft, administering the compound i.p. t.i.d. for 12 days. The treatments were also in this case well tolerated and TGI was 75% compared with controls[3].
作用机制 PHA-680632 inhibit autophosphorylation at Thr248 in the activation loop and process of binding to the CPC protein INCENP[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.99mL

0.40mL

0.20mL

9.97mL

1.99mL

1.00mL

19.94mL

3.99mL

1.99mL
参考文献

[1]Tao Y, Zhang P, et al. Enhancement of radiation response by inhibition of Aurora-A kinase using siRNA or a selective Aurora kinase inhibitor PHA680632 in p53-deficient cancer cells. Br J Cancer. 2007 Dec 17;97(12):1664-72.

[2]Soncini C, Carpinelli P, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9.

[3]Soncini C, Carpinelli P, Gianellini L, Fancelli D, Vianello P, Rusconi L, Storici P, Zugnoni P, Pesenti E, Croci V, Ceruti R, Giorgini ML, Cappella P, Ballinari D, Sola F, Varasi M, Bravo R, Moll J. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res. 2006 Jul 1;12(13):4080-9.

[4]Pollard JR, Mortimore M. Discovery and development of aurora kinase inhibitors as anticancer agents. J Med Chem. 2009 May 14;52(9):2629-51.