Uprosertib (GSK2141795)
別名: GSK795
Uprosertib (GSK2141795, GSK795)是一種選擇性的，ATP競爭性的，具有口服活性的Akt抑制劑，其對Akt 1/2/3的 IC50分別為180 nM, 328 nM和38 nM。Phase 2。
Uprosertib (GSK2141795) Chemical Structure
CAS: 1047634-65-0
產(chǎn)品質(zhì)控
批次：
純度：
99.84%
99.84
Uprosertib (GSK2141795)相關(guān)產(chǎn)品
相關(guān)信號通路圖
細胞實驗數(shù)據(jù)示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息(PMID) |
|---|---|---|---|---|---|
| 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 | ||
| 點擊查看更多細胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Uprosertib (GSK2141795, GSK795)是一種選擇性的，ATP競爭性的，具有口服活性的Akt抑制劑，其對Akt 1/2/3的 IC50分別為180 nM, 328 nM和38 nM。Phase 2。 | ||||||
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| 靶點 |
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| 體外研究(In Vitro) | ||||
| 體外研究活性 | Uprosertib抑制了BT474和LNCaP細胞中多個AKT底物的磷酸化水平。Uprosertib優(yōu)先的抑制了AKT通路活化的腫瘤細胞增殖。在細胞系LNCaP, BT474, A3和I9.2中，Uprosertib還導(dǎo)致了細胞周期停滯。 在SKOV3和PEO4細胞中，Uprosertib導(dǎo)致了生長停滯，并且增強了誘導(dǎo)的凋亡。 |
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|---|---|---|---|---|
| 激酶實驗 | 選擇性試驗 | |||
| 裂解液(5 mg總蛋白)分別用DMSO, 2.5 nM, 25 nM, 250 nM, 2.5 μM以及25 μM的抑制劑(GSK690693或者GSK2141795)處理，放到振蕩器上4 °C孵育45 min。雖有，將裂解液加入beads(偶聯(lián)有Akt探針)4 1 h，用于定性和定量實驗。將beads用1× CP緩沖液沖洗，并用離心收集。結(jié)合蛋白用2× NuPAGE LDS樣本緩沖液抽提，抽吸液用50 mM二硫蘇糖醇和55 mM碘乙酰胺處理。 | ||||
| 細胞實驗 | 細胞系 | 290個細胞系 | ||
| 濃度 | ~30 μM | |||
| 孵育時間 | 3 d | |||
| 方法 | 細胞系通常培養(yǎng)在加入10% FBS的RPMI 160培養(yǎng)基中。一部分細胞系生長在供應(yīng)商特殊處理的培養(yǎng)基中。用CellTiter-GloA來檢測 3-day增殖試驗中在化合物0–30 µM濃度下的生長抑制。細胞成長數(shù)據(jù)用DMSO處理的細胞作為空白對照。EC50利用4或者6個參數(shù)的抑制數(shù)據(jù)進行計算。 |
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| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | 在生長有BT474乳腺癌腫瘤的小鼠中，Uprosertib (100 mg/kg, p.o.)導(dǎo)致了61%的腫瘤生長抑制。在生長有SKOV3卵巢癌腫瘤小鼠中，Uprosertib (30 mg/kg, p.o.)也誘導(dǎo)了61%的腫瘤生長抑制。 |
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|---|---|---|
| 動物實驗 | Animal Models | 生長有BT474或者SKOV3腫瘤的小鼠 |
| 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 |
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化學(xué)信息&溶解度
| 分子量 | 429.25 | 分子式 | C18H16Cl2F2N4O2 |
| CAS號 | 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 | ||
| 儲存條件(自收到貨起) | |||
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體外溶解度 |
DMSO : 85 mg/mL ( (198.01 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Ethanol : 85 mg/mL (198.01 mM) Water : Insoluble |
摩爾濃度計算器 |
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體內(nèi)溶解配方 現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動物體內(nèi)配方計算器 | |||||
實驗計算
動物體內(nèi)配方計算器（澄清溶液）
第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）
mg/kg
g
μL
只
第二步：請輸入動物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計算結(jié)果：
工作液濃度： mg/ml；
DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；
體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。
體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。
注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。
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