| 中文名称: | PF-AKT400 | ||||
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| 英文名称: | PF-AKT400 | ||||
| 别名: | (S)-N-[[3-氨基-1-(5-乙基-7H-吡咯并[2,3-d]嘧啶-4-基)吡咯烷-3-基]甲基]-2,4-二氟苯甲酰胺;(S)-N-[[3-氨基-1-(5-乙基-7H-吡咯并[2,3-D]嘧啶-4-基)吡咯烷-3-基]甲基]-2,4-二氟苯甲酰胺 AKT protein kinase inhibitor;N-{[(3s)-3-Amino-1-(5-Ethyl-7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)pyrrolidin-3-Yl]methyl}-2,4-Difluorobenzamide | ||||
| CAS No: | 1004990-28-6 | 分子式: | C20H22F2N6O | 分子量: | 400.43 |
| CAS No: | 1004990-28-6 | ||||
| 分子式: | C20H22F2N6O | ||||
| 分子量: | 400.43 | ||||
基本信息
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产品编号： |
P11734 |
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产品名称： |
PF-AKT400 |
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CAS: |
1004990-28-6 |
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： |
400.43 |
-20℃ |
1个月 |
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化学名： |
AKT protein kinase inhibitor;N-{[(3s)-3-Amino-1-(5-Ethyl-7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)pyrrolidin-3-Yl]methyl}-2,4-Difluorobenzamide |
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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 |
2.4973mL |
12.4866mL |
24.9732mL |
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5mM |
0.4995mL |
2.4973mL |
4.9946mL |
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10mM |
0.2497mL |
1.2487mL |
2.4973mL |
生物活性
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产品描述 |
一种有效的,ATP竞争性的选择性Akt抑制剂，对PKBα(IC50=0.5nM)的选择性比PKA (IC50=450nM)高900倍。 |
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靶点 |
PKBα 0.5nM (IC50) |
PKA 450nM (IC50) |
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体外研究 |
PF-AKT400 (Compound 42) provides significantly enhanced selectivity for Akt relative to earlier leads such as spiroindoline 2.Free IC50 and EC50 values are estimated for phospho-S6 reduction (110nM) and Akt hyperphosphorylation (216nM),respectively.These values corresponded well to the cellular IC50 for PF-AKT400 in U87 cells measuring p-GSK-3α(310nM). |
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体内研究 |
PF-AKT400 is subsequently evaluated for modulation of Akt in tumors and in multiple in vivo mouse models of antitumor efficacy.It is active in a PC3 prostate carcinoma xenograft experiment,with 75% TGI observed at 100mg/kg b.i.d.dosing for 10 days.In a colorectal carcinoma (Colo205) xenograft study,PF-AKT400 produces 60% TGI at 150mg/kg b.i.d.after 10 days.Most intriguingly,in combination with Rapamycin (10mg/kg,ip),75mg/kg b.i.d.(10 days) of PF-AKT400 results in 98% TGI in an additional PC3 prostate carcinoma xenograft study compared to 56% TGI and 66% TGI with PF-AKT400 and Rapamycin as single agents.To define the in vivo potency of PF-AKT400 (Compound 42) in the PC3 xenograft model, oral administration of 25,75,and 100mg/kg PF-AKT400 is performed with blood and tumor sampling over time.Immunoblot analysis of detergentsoluble extracts derived from PC3 tumors shows a significant reduction of S6 phosphorylation,and hyperphosphorylation of Akt upon treatment at doses that produced significant tumor growth inhibition.Plasma drug concentrations peak rapidly after oral administration of doses between 25-100mg/kg (Tmax=0.5h).Peak PD responses of phospho-S6 and phospho-Akt are observed at approximately 2-4h and 1h post-administration of PF-AKT400,respectively.The time-course of PD marker response is well described by a PK/PD model at doses that ranged from no efficacy (25mg/kg) to maximal efficacy (100mg/kg). |
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推荐实验方法(仅供参考)
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激酶实验： |
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A fluorescence polarization IMAP type assay is used. An amount of 15μL of diluted PF-AKT400 (Compound 42) in DMSO is mixed with 60μL of reaction buffer (10mM Tris-HCl,pH 7.5,10mM MgCl2,0.1mM EGTA,0.01% Triton-X100,1mM DTT).Then 5μL of the compound/buffer mixture,10μL of a solution containing 4μM ATP and 40nM fluorescent-labeled Crosstide (Tamara-labeled GRPRTSSFAEG peptide),and 5μL of Akt1 protein (lacking the pleckstrin homology (PH) domain,containing an Asp at position 473,and prephosphorylated at Thr 308) in reaction buffer are combined.After a 90 min incubation,IMAP beads are added and plates are read (lamp filter,544nm;emission filter,615nm).The same procedure can be applied to full length Akt1 to provide similar results. All IC50 values are the geometric mean of at least n=2 determinations. |
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动物实验: |
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Mice Studies to describe the PK/PD relationship for PF-AKT400 are performed in male SCID/Beige mice bearing subcutaneous PC3 prostate carcinoma xenografts.Once tumors reach about ~300mm3 in size,PF-AKT400 is formulated in 0.5% methylcellulose vehicle and administered orally to 3 mice per dose group.Plasma and tumors are harvested over time,tumor lysates prepared,and the levels of phospho S6 reduction and phospho Akt induction are evaluated by immunoblot. |
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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 )
