Uprosertib (GSK2141795)
别名: GSK795
Uprosertib (GSK2141795, GSK795)是一种选择性的，ATP竞争性的，具有口服活性的Akt抑制剂，其对Akt 1/2/3的 IC50分别为180 nM, 328 nM和38 nM。Phase 2。
Uprosertib (GSK2141795) Chemical Structure
CAS: 1047634-65-0
客户使用Selleck的Uprosertib (GSK2141795)发表文献12篇
客户使用该产品的1个实验数据
产品质控
Uprosertib (GSK2141795)相关产品
| 相关靶点 | Akt1 Akt2 Akt3 | 点击展开 |
|---|---|---|
| 相关化合物库 | 激酶抑制剂库 PI3K/Akt 抑制剂库 凋亡分子化合物库 细胞周期化合物库 NF-κB信号通路库 | 点击展开 |
相关信号通路图
Akt抑制剂选择性比较
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| Sf9 | Function assay | 40 mins | Inhibition of full length human AKT2 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50=0.01585μM | ChEMBL | |
| Sf9 | Function assay | 40 mins | Inhibition of full length human AKT1 expressed in Sf9 cells assessed as reduction in substrate phosphorylation using biotin-ahx-ARKRERAYSFGHHA-amide substrate and [gamma-33P]ATP incubated for 40 mins by top count microplate scintillation counting method, IC50=0.001995μM | ChEMBL | |
| OVCAR8 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM | 31301565 | |
| HCT116 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM | 31298542 | |
| PTEN-null LNCAP | Function assay | 1 hr | Inhibition of Akt in human PTEN-null LNCAP cells assessed as suppression in PRAS40 phosphorylation after 1 hr by ELISA analysis, IC50=0.07563μM | 27089211 | |
| HCT116 | Growth inhibition assay | 72 hrs | Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay | 31301565 | |
| OVCAR8 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human OVCAR8 cells assessed as reduction in cell viability incubated for 72 hrs by SRB assay, IC50=0.54μM | 31301565 | |
| HCT116 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HCT116 cells after 72 hrs by SRB assay, IC50=0.72μM | 31298542 | |
| HCT116 | Growth inhibition assay | 72 hrs | Growth inhibition of human HCT116 cells over-expressing DHODH at 2 times antiproliferative IC50 after 72 hrs in absence of uridine by MTT assay | 31301565 | |
| RPMI8226 | Antiproliferative assay | Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM | 31301565 | ||
| MM1S | Antiproliferative assay | Antiproliferative activity against human MM1S cells assessed as reduction in cell viability, IC50=0.032μM | 31301565 | ||
| CEM/C1 | Antiproliferative assay | Antiproliferative activity against human CEM/C1 cells assessed as reduction in cell viability, IC50=0.03μM | 31301565 | ||
| HUT78 | Antiproliferative assay | Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM | 31301565 | ||
| KB-3-1 | qHTS assay | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | ChEMBL | ||
| JVM2 | Antiproliferative assay | Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM | 31301565 | ||
| OVCAR8 | Antiproliferative assay | Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM | 31298542 | ||
| MOLT4 | Antiproliferative assay | Antiproliferative activity against human MOLT4 cells assessed as reduction in cell viability, IC50=0.066μM | 31301565 | ||
| MV4-11 | Antiproliferative assay | Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM | 31301565 | ||
| LNCAP | Antiproliferative assay | Antiproliferative activity against human LNCAP cells, IC50=0.07μM | 31298542 | ||
| U937 | Antiproliferative assay | Antiproliferative activity against human U937 cells assessed as reduction in cell viability, IC50=0.101μM | 31301565 | ||
| OVCAR8 | Antiproliferative assay | Antiproliferative activity against human OVCAR8 cells, IC50=0.24μM | 31298542 | ||
| JVM2 | Antiproliferative assay | Antiproliferative activity against human JVM2 cells assessed as reduction in cell viability, IC50=0.293μM | 31301565 | ||
| HUT78 | Antiproliferative assay | Antiproliferative activity against human HUT78 cells assessed as reduction in cell viability, IC50=0.378μM | 31301565 | ||
| RPMI8226 | Antiproliferative assay | Antiproliferative activity against human RPMI8226 cells assessed as reduction in cell viability, IC50=0.538μM | 31301565 | ||
| MV4-11 | Antiproliferative assay | Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability, IC50=0.635μM | 31301565 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Uprosertib (GSK2141795, GSK795)是一种选择性的，ATP竞争性的，具有口服活性的Akt抑制剂，其对Akt 1/2/3的 IC50分别为180 nM, 328 nM和38 nM。Phase 2。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | Uprosertib抑制了BT474和LNCaP细胞中多个AKT底物的磷酸化水平。Uprosertib优先的抑制了AKT通路活化的肿瘤细胞增殖。在细胞系LNCaP, BT474, A3和I9.2中，Uprosertib还导致了细胞周期停滞。[2] 在SKOV3和PEO4细胞中，Uprosertib导致了生长停滞，并且增强了cisplatin诱导的凋亡。[3] | |||
|---|---|---|---|---|
| 激酶实验 | 选择性试验 | |||
| 裂解液(5 mg总蛋白)分别用DMSO, 2.5 nM, 25 nM, 250 nM, 2.5 μM以及25 μM的抑制剂(GSK690693或者GSK2141795)处理，放到振荡器上4 °C孵育45 min。虽有，将裂解液加入beads(偶联有Akt探针)4 1 h，用于定性和定量实验。将beads用1× CP缓冲液冲洗，并用离心收集。结合蛋白用2× NuPAGE LDS样本缓冲液抽提，抽吸液用50 mM二硫苏糖醇和55 mM碘乙酰胺处理。 | ||||
| 细胞实验 | 细胞系 | 290个细胞系 | ||
| 浓度 | ~30 μM | |||
| 孵育时间 | 3 d | |||
| 方法 | 细胞系通常培养在加入10% FBS的RPMI 160培养基中。一部分细胞系生长在供应商特殊处理的培养基中。用CellTiter-GloA来检测 3-day增殖试验中在化合物0–30 µM浓度下的生长抑制。细胞成长数据用DMSO处理的细胞作为空白对照。EC50利用4或者6个参数的抑制数据进行计算。 | |||
| 体内研究(In Vivo) | ||
| 体内研究活性 | 在生长有BT474乳腺癌肿瘤的小鼠中，Uprosertib (100 mg/kg, p.o.)导致了61%的肿瘤生长抑制。在生长有SKOV3卵巢癌肿瘤小鼠中，Uprosertib (30 mg/kg, p.o.)也诱导了61%的肿瘤生长抑制。[2] | |
|---|---|---|
| 动物实验 | Animal Models | 生长有BT474或者SKOV3肿瘤的小鼠 |
| Dosages | 100 mg/kg | |
| Administration | p.o. | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01958112 | Terminated | Cervical Cancer |
Dana-Farber Cancer Institute|Novartis|National Comprehensive Cancer Network |
October 2013 | Phase 2 |
| NCT01941927 | Completed | Melanoma |
Adil Daud|National Comprehensive Cancer Network|University of California San Francisco |
September 10 2013 | Phase 2 |
| NCT01266954 | Completed | Solid Tumours |
GlaxoSmithKline |
June 1 2010 | Phase 1 |
| NCT01138085 | Completed | Cancer |
GlaxoSmithKline |
May 4 2010 | Phase 1 |
化学信息&溶解度
| 分子量 | 429.25 | 分子式 | C18H16Cl2F2N4O2 |
| CAS号 | 1047634-65-0 | SDF | Download Uprosertib (GSK2141795) SDF |
| Smiles | CN1C(=C(C=N1)Cl)C2=C(OC(=C2)C(=O)NC(CC3=CC(=C(C=C3)F)F)CN)Cl | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 85 mg/mL ( (198.01 mM)； DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 85 mg/mL Water : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
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）
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）
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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