中文名称: | PF-4989216 | ||||
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英文名称: | PF-4989216 | ||||
别名: | 4-(4-氰基-2-氟苯基)-2-吗啉-5-(1H-1,2,4-三唑-5-基)噻吩-3-腈 PF-4989216 | ||||
CAS No: | 1276553-09-3 | 分子式: | C18H13FN6Os | 分子量: | 380.4 |
CAS No: | 1276553-09-3 | ||||
分子式: | C18H13FN6Os | ||||
分子量: | 380.4 |
基本信息
产品编号: |
P10826 |
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产品名称: |
PF-4989216 |
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CAS: |
1276553-09-3 |
储存条件 |
粉末 |
-20℃ |
四年 |
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分子式: |
溶于液体 |
-80℃ |
6个月 |
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分子量: |
380.40 |
-20℃ |
1个月 |
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化学名: |
4-(4-cyano-2-fluorophenyl)-2-morpholin-4-yl-5-(1H-1,2,4-triazol-5-yl)thiophene-3-carbonitrile |
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Solubility (25°C): |
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体外:
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DMSO |
76mg/mL (199.78mM) |
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Ethanol |
7mg/mL warmed with 50ºC water bath (18.4mM) |
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Water |
Insoluble |
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体内(现配现用): |
Suspended in 0.5% methylcellulose |
1mg/mL |
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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。 |
制备储备液
浓度
溶液体积 质量 |
1mg |
5mg |
10mg |
1mM |
2.6288mL |
13.1441mL |
26.2881mL |
5mM |
0.5258mL |
2.6288mL |
5.2576mL |
10mM |
0.2629mL |
1.3144mL |
2.6288mL |
生物活性
产品描述 |
一种有效的选择性PI3Kα抑制剂,Ki为0.6nM。 |
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靶点 |
PI3Kα 0.6nM (Ki) |
Mtor 1440 nM (Ki) |
体外研究 |
PF-4989216 (Compound 10) has excellent PI3KαKi (0.6nM),good cellular potency (S473 IC50=79nM),and good selectivity against mTOR (mTOR Ki=1440nM).PF-4989216 has PI3KαKi less than 1nM and mTOR Ki more than 1μM.PF-4989216 also has excellent selectivity over 40 other kinases,and no major CYP inhibitions are observed.Less than 30% inhibition is observed in 1A2,2C9,2D6,and 3A4 CYP enzymes at 3μM.The toxicity of PF-4989216 in several drug-sensitive and MDR cancer cell lines,including cells overexpressing ABCB1 or ABCG2,and in HEK293 cells transfected with human ABCB1 or ABCG2 is determined.PF-4989216 inhibits human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80 with IC50s of 1.11±0.09 and 6.79±1.00uM,respectively.PF-4989216 inhibits human breast carcinoma MCF-7 and ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 IC50s of 2.30±0.68,23.26±2.94 and 62.57±5.46uM,respectively.PF-4989216 inhibits pcDNA-HEK293,ABCB1-transected MDR19-HEK293,ABCG2-tranfected R482-HEK293 cells with IC50s of 0.44±0.05,0.38±0.06 and 5.05±0.89uM,respectively. |
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体内研究 |
PF-4989216 (Compound 10) is dosed orally in our in vivo antitumor model,PI3K driven NCI-H1975 xenograft tumors.PF4989216 demonstrates dose responsive tumor growth inhibitory activity from 25 to 200mg/kg in QD oral dosing. |
推荐实验方法(仅供参考)
细胞实验: |
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MTT and CCK-8 assays are performed to determine the general sensitivities of cells to the tested drugs.The human colon carcinoma S1 cell line and ABCG2-overexpressing subline S1-M1-80 are treated with PF-4989216 (0.1,1 and 10μM).The human breast carcinoma MCF-7 and ABCG2-overexpressing sublines MCF7-FLV1000 and MCF7-AdVp3000 are treated with PF-4989216 (0.1,1,10 and 100μM).The parental HEK293 and ABCG2-tranfected R482-HEK293 cells are treated with PF4989216 (0.01,0.1,1 and 10μM).For the reversal of cytotoxicity assays,PF-4989216 or Ko143 or Lapatinib at a nontoxic concentration is added into the cytotoxicity assay,and the extent of reversal is then calculated. |
动物实验: |
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Mice For animal studies,6-8 week old nu/nu athymic female mice are used.Tumors are established by injecting 2×106 cells suspended 1:1 (v/v) with reconstituted basement membrane.For tumor growth inhibition studies,mice with established tumors of ~150 mm3 are randomized.PF-4989216 (Compound 10) is dosed orally (25,50,100 and 200mg/kg) in a mouse PI3K driven NCI-H1975 xenograft tumor model.Tumor dimensions are measured with vernier calipers,and tumor volumes are calculated.Tumor growth inhibition percentage (TGI%) is calculated. |
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 )