Uprosertib (GSK2141795)

别名: GSK795

目录号：S7492 Purity: 99.84%

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

规格	价格	库存
10mM (1mL in DMSO)	1122.03	现货
5mg	958.71	现货
25mg	3252.14	现货
100mg	7347.21	现货
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产品质控

批次：纯度： 99.84%

99.84

Uprosertib (GSK2141795)相关产品

相关靶点	Akt1 Akt2 Akt3	点击展开
相关产品	MK-2206 2HCl Perifosine SC79 Capivasertib (AZD5363) GSK690693 Ipatasertib (GDC-0068) Triciribine (API-2) CCT128930 Afuresertib (GSK2110183) A-674563 HCl AT7867 Oridonin Akti-1/2 PHT-427 TIC10 (ONC201) Miransertib (ARQ 092) HCl AT13148 Miransertib (ARQ-092) SC66 Deguelin ML-9 HCl	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

细胞实验数据示例

细胞系	实验类型	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

Akt3 ^[1] (Cell-free assay)	Akt1 ^[1] (Cell-free assay)	Akt2 ^[1] (Cell-free assay)
38 nM	180 nM	328 nM

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，并且增强了诱导的凋亡。^[3]
激酶实验	选择性试验
激酶实验	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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考文献
[1] Pachl F, et al. J Proteome Res. 2013, 12(8), 3792-3800. [2] Dumble M, et al. PLoS One. 2014, 9(6):e100880. [3] Cheraghchi-Bashi A, et al. Oncotarget. 2015, 6(39), 41736-41749.

参考文献

化学信息&溶解度

分子量	429.25	分子式	C₁₈H₁₆C_l2F₂N₄O₂
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)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

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 (198.01 mM)

Water : Insoluble

DMSO : 93 mg/mL ( (216.65 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 93 mg/mL (216.65 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解度
批次：

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

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

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 μL 动物数量只

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

%DMSO+ %

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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