Afuresertib (GSK2110183)

For research use only. Not for use in humans.

目录号:S7521 中文名称:阿氟色替

Afuresertib (GSK2110183) Chemical Structure

CAS No. 1047644-62-1

Afuresertib (GSK2110183)是一种有效的,口服生物可利用的 Akt 抑制剂,对Akt1,Akt2,和 Akt3 的 Ki 分别为 0.08 nM,2 nM,和 2.6 nM。Phase 2。

规格 价格 库存 购买数量  
RMB 1178.88 现货
RMB 3890.83 现货
RMB 8169.54 现货
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客户使用Selleck生产的Afuresertib (GSK2110183)发表文献17篇:

客户使用该产品的1个实验数据:

  • Analysis of the mechanism of action of the enhanced anti‑tumor effect of the combination therapy of suboptimal doses of pomalidomide plus dexamethasone and afuresertib in MM cells. (A‑C) The altered expression of protein substrates was analyzed in two MM cell lines that were treated with suboptimal doses of PD, or AFU, or the PD and AFU combination. The XG‑7 and U266 cell lines were subjected to the indicated treatments for 48 and 72 h, respectively. (A) Caspases, (B) substrates related mainly to the working mechanism of IMiDs, (C) substrates mainly related to the working mechanism of afuresertib, and (D) two primary MM cell cultures, were subjected to the analysis in the same manner as the two MM cell lines. In the expression panel of p‑FoxO3a/FoxO1, the upper band represents p‑FoxO3a and the lower band represents p‑FOXO1. PD, pomalidomide plus dexamethasone; AFU, Afuresertib; MM, multiple myeloma; IMiDs, immunomodulatory drugs.

    ONCOLOGY LETTERS, 2018, https://doi.org/10.3892/ol.2018.8501. Afuresertib (GSK2110183) purchased from Selleck.

产品安全说明书

Akt抑制剂选择性比较

生物活性

产品描述 Afuresertib (GSK2110183)是一种有效的,口服生物可利用的 Akt 抑制剂,对Akt1,Akt2,和 Akt3 的 Ki 分别为 0.08 nM,2 nM,和 2.6 nM。Phase 2。
靶点
Akt1 [1]
(Cell-free assay)
Akt2 [1]
(Cell-free assay)
Akt3 [1]
(Cell-free assay)
0.08 nM(Ki) 2 nM(Ki) 2.6 nM(Ki)
体外研究

Afuresertib抑制E17K AKT1突变蛋白的激酶活性,EC50为0.2 nM。Afuresertib对多重AKT底物磷酸化水平,包括GSK3b,PRAS40,FOXO和Caspase 9,表现出浓度依赖性作用。总体65%的血液学细胞系对afuresertib (EC50 < 1 μM)敏感。在测试的实体肿瘤细胞系中,21%对afuresertib的响应具有< 1 μM 的EC50 。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-GSK3 / GSK3 / p-PRAS40 / PRAS40 / p-FOXO / p-Casp9 / p-AKT / AKT / p-MEK / p-ERK / Erk ; 

PubMed: 24978597     


BT474 (left) and LNCaP (right) cell lines were treated with DMSO or GSK2110183 for 1 h. Western analysis was performed to assay levels of phosphorylated and total GSK-3, PRAS40, AKT and ERK, phosphorylated Foxo, Caspase 9, and MEK. Tubulin was used as a loading control. 

ATG3 / ATG12 / LC3B ; 

PubMed: 30867818     


Alterations in autophagy-related proteins induced by AKT inhibition.

24978597 30867818
体内研究 负荷BT474乳腺肿瘤异种移植物的小鼠,afuresertib (p.o.)以每天10,30或100 mg/kg的剂量给药,分别导致8,37和61% TGI。负荷SKOV3卵巢肿瘤异种移植物的小鼠用10,30和100 mg/kg afuresertib处理,分别导致23,37 和97% TGI。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

Afuresertib的效力(Ki*)测定:

抑制剂的真实效力(Ki*)首先在较低酶浓度(0.1 nM AKT1,0.7 nM AKT2,和0.2 nM AKT3)下使用过滤结合分析法测定,然后通过反应发展曲线分析证实。在过滤结合分析法中,酶的预混合物加抑制剂培养1小时,然后加入GSKα多肽 (Ac-KKGGRARTSS-FAEPG-amide)和 [γ33P] ATP。2小时后,反应终止,放射性标记的AKT多肽产物在磷酸纤维素过滤板上捕获。反应进展曲线分析利用连续实时荧光检测Sox-AKT-tide底物(Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2)生成的产品。
细胞实验:[1]
- 合并
  • Cell lines: 血液病细胞系和实体肿瘤癌细胞系
  • Concentrations: 30 μM
  • Incubation Time: 72 h
  • Method: 为期3天的增殖试验使用CellTiter-Glo进行,以测量0-30 μM化合物引起的生长抑制,细胞生长情况相对于未处理的(DMSO)对照组测定。EC50值根据抑制曲线使用Assay Client application中4或6参数拟合算法计算。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 负荷SKOV3或BT474肿瘤的雌性无胸腺裸鼠和 SCID小鼠
  • Dosages: 100 mg/kg
  • Administration: p.o.
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 85 mg/mL (198.91 mM)
Ethanol 85 mg/mL (198.91 mM)
Water Insoluble

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 427.32
化学式

C18H17Cl2FN4OS

CAS号 1047644-62-1
储存条件 粉状
溶于溶剂
别名 N/A

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

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 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

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 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、SDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04374630 Recruiting Drug: Paclitaxel|Drug: Afuresertib Platinum-resistant Ovarian Cancer Laekna Limited June 9 2020 Phase 2
NCT04060394 Recruiting Drug: Phase I and Phase II: LAE001/prednisone + afuresertib Metastatic Castration-resistant Prostate Cancer Laekna Limited September 13 2019 Phase 1|Phase 2
NCT02235740 Terminated Drug: Afuresertib|Drug: Carfilzomib Cancer Novartis|Amgen November 2014 Phase 1
NCT02240212 Completed Drug: Afuresertib|Drug: Paclitaxel Cancer Novartis Pharmaceuticals|Novartis October 2014 Phase 1
NCT02177682 Terminated Drug: Afuresertib Neoplasms Haematologic Novartis Pharmaceuticals|Novartis August 13 2014 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID