BEZ235CAS号: 915019-65-7分子式: C30H23N5O分子量: 469.55描述纯度储存/保存方法别名外观可溶性/溶解性靶点In vitro(体外研究)In vivo(体内研究)参考文献
产品描述 | |
描述 |
BEZ235 (NVP-BEZ235, Dactolisib) 是一种双重ATP竞争性 PI3K 和 mTOR 抑制剂,在无细胞试验中,抑制 p110α/γ/δ/β 和 mTOR(p70S6K) 的 IC50 分别为 4 nM /5 nM /7 nM /75 nM /6 nM。 在 3T3TopBP1-ER 细胞中抑制 ATR,IC50 为 21 nM,而对 Akt 和 PDK1 的抑制作用很弱。 |
纯度 |
>98%
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储存/保存方法 |
Store at -20℃ for one year(Powder);Store at 2-4℃ for two weeks;Store at -20℃ for six months after dissolution.
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基本信息 | |
别名 |
NVP-BEZ 235;BEZ-235;BEZ 235;NVP-BEZ235;Dactolisib
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外观 |
White powder
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可溶性/溶解性 |
DMF :18 mg/mL warmed (38.33 mM)
DMSO : 5.2 mg/mL (11.07 mM; Need ultrasonic and warming) |
生物活性 | |
靶点 |
p110α;p110γ;mTOR (p70S6K);p110δ;ATR
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In vitro(体外研究) |
BEZ235 significantly reduces the phosphorylation levels of the mTOR activated kinase p70S6K. BEZ235 results in a reduction of S235/S236P-RPS6 levels with IC50 of 6.5 nM. The activity of BEZ235 against mTOR is determined using a biochemical mTOR K-LISA assay with IC50 of 20.7 nM. BEZ235 shows slightly lower activity against its β paralogue with IC50 of 75 nM. The PI3K/Akt/mTOR pathway is often constitutively activated in human tumor cells. BEZ235 blocks PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. Both PTEN-null cell lines PC3M and U87MG show a dose-dependent reduction in cell proliferation when treated with increasing concentrations of BEZ235 with an average GI50 of 10-12 nM. BEZ235 is an mTORC1/2 catalytic inhibitor.
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In vivo(体内研究) |
BEZ235 induces regression of the tumors (69%) without statistically significant effect on body weight gain. Altogether, these preliminary in vivo efficacy results show that BEZ235 causes disease stasis when administered orally as a single agent and can enhance the efficacy of other anticancer agents when used in combination studies.
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参考文献 | |
参考文献 |
[1] Maira SM, et al. Mol Cancer Ther, 2008, 7(7), 1851-1863. [2] Roper J, et al. PLoS One, 2011, 6(9), e25132. [3] Roulin D, et al. Mol Cancer, 2011, 10, 90. [4] Cho DC, et al. Clin Cancer Res, 2010, 16(14), 3628-3638. [5] Zhang Y, et al. J Cell Physiol, 2012, 227(1), 35-43. [6] Shoji K, et al. PLoS One, 2012, 7(5), e37431. [7] Chiarini F, et al. Cancer Res, 2010, 70(20), 8097-8107. [8] Toledo LI, et al. Nat Struct Mol Biol, 2011, 18(6), 721-727. |
分子结构图