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FRAX1036

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Chemical Structure| 1432908-05-8 同义名 : -
CAS号 : 1432908-05-8
货号 : A374154
分子式 : C28H32ClN7O
纯度 : 99%+
分子量 : 518.053
MDL号 : MFCD30187513
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 4 mg/mL(7.72 mM)，配合水浴加热至45℃助溶，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

  • PAK

    PAK2, Ki:72.4 nM

    PAK4, Ki:23.3 nM

  • PAK1

    PAK1, Ki:23.3 nM

  • PAK2

    PAK2, Ki:72.4 nM

  • PAK4

    PAK4, Ki:2.4 μM
描述 The p21-activated kinases (PAKs) have generated significant interest as therapeutic targets in cancer. PAK1 signaling has been shown to be important for regulating cytoskeletal organization and cell migration via both its catalytic activity and protein-protein interactions. FRAX1036, a small molecule pyridopyrimidinone, is a PAK inhibitor. Its biochemical potency (Ki) against PAK1 and PAK2 is 23.3 and 72.4 nM, respectively, with high selectivity against PAK4. Potent cellular inhibition of group I PAK substrate phosphorylation was observed at 2.5 to 5 μM concentrations of FRAX1036 in PAK1-amplified MDA-MB-175 cells. FRAX1036 (5 μM) and docetaxel (0.2 μM) combination treatment for 24 hours of PAK1-amplified lines, MDA-MB-175 and HCC2911, elevated a major apoptotic marker (cleaved PARP) and attenuated a cell cycle regulator (cyclin D1). After 20 hours of treatment with 2.5 μM FRAX1036 for 20 hours, microtubules were disorganized and were not evenly distributed throughout the cytoplasm, between the microtubule organizing center and the periphery. Furthermore, FRAX1036-treated cells completed normal mitoses with the majority of apoptosis occurring during interphase (66.7%)[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.65mL

1.93mL

0.97mL

19.30mL

3.86mL

1.93mL
参考文献

[1]Ong CC, Gierke S, et al. Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Res. 2015 Apr 23;17:59.

[2]Kosoff RE, Aslan JE, et al. Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization. Blood. 2015 May 7;125(19):2995-3005.

[3]Ong CC, Gierke S, Pitt C, et al. Small molecule inhibition of group I p21-activated kinases in breast cancer induces apoptosis and potentiates the activity of microtubule stabilizing agents. Breast Cancer Res. 2015;17(1):59