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A66

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Chemical Structure| 1166227-08-2 同义名 : -
CAS号 : 1166227-08-2
货号 : A102947
分子式 : C17H23N5O2S2
纯度 : 99%+
分子量 : 393.527
MDL号 : MFCD22378485
存储条件：

粉末 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: 50 mg/mL(127.06 mM)，配合低频超声助溶，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

  • C2β

    C2β, IC50:462 nM

  • p110α

    p110α, IC50:32 nM
描述 The three class-Ia PI3Ks (phosphoinositide 3-kinases; p110α/p110β/p110δ) and the sole class-Ib PI3K (p110γ) couple growth factor receptors and G-protein-coupled receptors to a wide range of downstream pathways, they all use PtdIns(4,5)P2 to produce PtdIns(3,4,5)P3. The cellular levels of PtdIns(3,4,5)P3 are tightly controlled by phosphatases, including PTEN (phosphatase and tensin homologue deleted on chromosome 10) which dephosphorylates PtdIns(3,4,5)P3 back to PtdIns(4,5) P2. The importance of this pathway in cancer is highlighted by the fact that defects in both the kinase and phosphatase activities are commonly observed in tumours. A66 is a highly selective and specific p110α inhibitor with IC50 value of 32 nM in the cell-free assay. The effect of the A66 S form was tested on SK-OV-3 tumour tissue in vivo using a single dose of 100 mg/kg of body weight to determine whether a long-lasting effect of the drug could be achieved on target tissues. A66 S caused a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase at both 1 and 6 h after dosing. This is consistent with A66 S having a full inhibitory effect on PI3K signalling in the tumours during this time. A66 S was dosed QD at 100 mg/kg of body weight for up to 21 days or BID at 75 mg/kg of body weight for 16 days in tumour efficacy studies. Both dosing strategies induced a significant delay in growth of SK-OV-3 xenografted tumours. At the final day of dosing, the average TGI (tumour growth inhibition) for A66 S form was 45.9% of control (QD; P<0.05) and 29.9% of control (BID; P<0.01)[3].
作用机制 The carboxamide amine moiety forms hydrogen bonds with the side-chain carbonyl group of Gln859 and possibly the backbone carbonyl group of Ser854[3].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.54mL

0.51mL

0.25mL

12.71mL

2.54mL

1.27mL

25.41mL

5.08mL

2.54mL
参考文献

[1]Jamieson S, Flanagan JU, et al. A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types. Biochem J. 2011 Aug 15;438(1):53-62.

[2]Sun M, Hillmann P, et al. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15547-52.

[3]A drug targeting only p110α can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types