| 中文名称: | A66 | ||||
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| 英文名称: | A66 | ||||
| 别名: | (S)-N1-(2-叔丁基)-4'-甲基-[4,5'-二噻唑基] -2'-基)吡咯烷-1,2-二甲酰胺 (2S)-N1-[5-(2-Tert-butyl-4-thiazolyl)-4-methyl-2-thiazolyl]pyrrolidine-1,2-dicarboxamide | ||||
| CAS No: | 1166227-08-2 | 分子式: | C17H23N5O2S2 | 分子量: | 393.53 |
| CAS No: | 1166227-08-2 | ||||
| 分子式: | C17H23N5O2S2 | ||||
| 分子量: | 393.53 | ||||
基本信息
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产品编号： |
A12814 |
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产品名称： |
A66 |
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CAS: |
1166227-08-2 |
储存条件 |
粉末 |
-20℃ |
四年 |
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4℃ |
四年 |
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分子式： |
溶于液体 |
-80℃ |
6个月 |
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分子量： |
393.53 |
-20℃ |
1个月 |
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化学名： |
(2S)-N1-[5-(2-Tert-butyl-4-thiazolyl)-4-methyl-2-thiazolyl]pyrrolidine-1,2-dicarboxamide |
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Solubility (25°C)： |
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体外:
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DMSO |
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Ethanol |
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Water |
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体内(现配现用): |
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＜1mg/ml表示微溶或不溶。 |
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普西唐提供的所有化合物浓度为内部测试所得，实际溶液度可能与公布值有所偏差，属于正常的批间细微差异现象。 |
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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 |
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制备储备液
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浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
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1mM |
2.5411mL |
12.7055mL |
25.4110mL |
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5mM |
0.5082mL |
2.5411mL |
5.0822mL |
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10mM |
0.2541mL |
1.2706mL |
2.5411mL |
生物活性
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产品描述 |
一种高特异性的选择性的p110α抑制剂，IC50为32nM。 |
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靶点 |
PI3K |
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体外研究 |
A66 is a potent inhibitor of the wild-type and oncogenic forms of p110α but not other class-I PI3K isoforms.The p110αspecific inhibitor A66 (0.7μM) induces a 75-80% reduction in focus formation by the highly transforming iSH2 mutants KS459delN,DKRMNS560del,and K379E.The p110α-specific inhibitor A66 reduced phosphorylation of Akt on T308 by all p85 mutants. |
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体内研究 |
The optimal dosing strategy for xenograft studies is determined by investigating the drug pharmacokinetics after a dose of 10mg/kg of body weight by intraperitoneal injection in CD-1 mice.Despite a short half-life of only 0.42h,the large Cmax (8247nM) of A66 S that is reached 30 min after dosing ensured that the AUC0-inf (area under the curve from zero time to infinity) (6809nM•h) is similar to that of BEZ-235 (7333nM•h),which has a longer half-life of 2.73h.Furthermore,the A66 on SK-OV-3 tumour tissue is tested using a single dose of 100mg/kg of body weight to determine whether a long-lasting effect of the drug could be achieved on target tissues.These studies show that A66 causes a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase,but not of ERK (extracellular-signal-regulated kinase),at both 1 and 6 h after dosing.Levels of A66 in plasma are determined to be 21.1±1.2μM and 9.1±1.1μM at 1 and 6h after drug injection,whereas levels of A66 in the tumor are 22.7±2.1μM and 16.0±1.3μM at the same time points. |
推荐实验方法(仅供参考)
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激酶实验： |
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IC50 values are evaluated using the PI3K (human) HTRF Assay. p85α/p110δ is obtained from Invitrogen.All other isoforms are produced in-house by co-expressing full-length human p85α with the indicated human full-length catalytic subunit containing a histidine tag at the N-terminus to allow purification.The PI3Ks are titrated and used at a concentration between their EC65-EC80 values.PI3K activity in immunoprecipitates is assayed using an antibody to the N-SH2 (N-Src homology 2) domain of p85α.Assays for other lipid kinases and protein kinases are performed by the National Centre for Protein Kinase Profiling and Invitrogen Drug Discovery Services. |
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动物实验: |
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Mice Age-matched specific pathogen-free Rag1-/- or NIH-III mice are subcutaneously inoculated on the right flank with 5×106 U87MG,SK-OV-3 or HCT-116 cells in PBS.Tumour diameter as measured by electronic calipers is used to calculate tumour volume (mm3) based on the formula (L×w2)×π/6 (where L=longest tumour diameter and w=perpendicular diameter).A66 is administered in 20% 2-hydroxypropyl-β-cyclodextrin in water,whereas BEZ-235 is administered in 10% ethanol.Control mice are administered the A66 dosing vehicle alone.The drugs are dosed by intraperitoneal injection as the free base equivalent at a dosing volume of 10mL/kg of body weight.For tumour pharmacodynamic studies,mice are administered a single dose of A66 or the control vehicle when tumors reached approximately 8-9 mm in diameter. Animals are killed 1 or 6h after dosing and the tumors are removed,biopulverized and assayed for protein concentration.For antitumor efficacy studies,dosing began when tumors are well established,averaging approximately 7 mm in diameter.Doses are administered once daily (QD) or twice daily (BID) with injections separated by a minimum of approximately 8 h. Different dosing schedules are used for the three xenograft models depending on the rate of tumor growth and the body weight tolerance of control mice.Animals are dosed daily for 21 days or twice daily for 16 days (SK-OV-3),daily for 14 days (U87MG) and daily for 7 days (HCT-116).Animals are monitored daily for any signs of emerging toxicity and body weight is recorded.Mice are killed if they developed moderate signs of toxicity or if body weight loss exceeded 20% of starting weight.TGI (tumour growth inhibition) is calculated on the final day of dosing by determining the relative tumour size of drug-treated mice as a percentage of the average relative tumour size of control mice.The statistical significance of TGI values is determined by one-way ANOVA with Bonferroni multiple comparison analysis using GraphPad Prism 5.02. |
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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：
质量 (g) = 浓度 (mol/L) x 体积 (L) x 分子量 (g/mol)
摩尔浓度计算公式
用本工具协助配置特定浓度的溶液，使用的计算公式为：
开始浓度 x 开始体积 = 最终浓度 x 最终体积
稀释公式
稀释公式一般简略地表示为：C1V1 = C2V2 ( 输入 输出 )
