Omipalisib (GSK2126458)
别名: GSK458
Omipalisib (GSK2126458, GSK458)是一种高选择性的，有效的p110α/β/γ/δ和 mTORC1/2抑制剂，无细胞试验中Ki分别为0.019 nM/0.13 nM/0.024 nM/0.06 nM和0.18 nM/0.3 nM。Omipalisib 可诱导自噬。Phase 1。
Omipalisib (GSK2126458) Chemical Structure
CAS: 1086062-66-9
产品质控
批次：
纯度：
99.46%
99.46
Omipalisib (GSK2126458)相关产品
相关信号通路图
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 |
|---|---|---|---|---|---|
| HCT116 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 0.01 μM. | 26819001 | |
| Bel7404 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human Bel7404 cells after 72 hrs by MTT assay, IC50 = 0.01 μM. | 26819001 | |
| MDA-MB-231 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50 = 0.13 μM. | 26819001 | |
| A549 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.14 μM. | 27448924 | |
| HCT116 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50 = 0.154 μM. | 27448924 | |
| U87MG | Cytotoxicity assay | 72 hrs | Cytotoxicity against human U87MG cells after 72 hrs by MTT assay, IC50 = 0.537 μM. | 27448924 | |
| A549 | Cytotoxicity assay | 72 hrs | Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50 = 0.6 μM. | 26819001 | |
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) | 29435139 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells | 29435139 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Omipalisib (GSK2126458, GSK458)是一种高选择性的，有效的p110α/β/γ/δ和 mTORC1/2抑制剂，无细胞试验中Ki分别为0.019 nM/0.13 nM/0.024 nM/0.06 nM和0.18 nM/0.3 nM。Omipalisib 可诱导自噬。Phase 1。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | GSK2126458有效抑制人类癌细胞中发现的p110α(E542K, E545K, 和H1047R)常见激活突变型，Ki 分别为 8 pM, 8 pM 和 9 pM。GSK2126458作用于T47D和BT474 细胞，显著降低pAKT-S473水平，IC50分别为 0.41 nM 和 0.18 nM。 而且, GSK2126458作用于多种细胞系，包括T47D 和 BT474乳腺癌细胞系，导致细胞周期停在G1期，且抑制细胞增殖，IC50分别为3 nM 和2.4 nM。[1] | |||
|---|---|---|---|---|
| 激酶实验 | 体外均相时间分辨荧光技术（HTRF）测定 PI3K 抑制 | |||
| 在384孔聚丙烯母板上，化合物 (3倍溶于100% DMSO) 从1列到12列，和13列到24列连续稀释，获得11种浓度 GSK2126458。6列和18列只含DMSO。滴定后，0.05μL 立即转移到384孔低容量实验板上。 实验板中含3种药物对照(PI3K 抑制剂)和3组实验对照: (1) 不含抑制剂的酶实验;(2) 去酶buffer, 和 (3)去酶加 PIP3的buffer。DMSO加到6列和18列的所有孔中。40 μM PIP3加到 1X 反应 buffer (1μL 200 μM PIP3)中， 交替 18列的行数 ( B, D, F, H, J, L, N, P)。不含酶的对照实验在 A, C, E, G, I, K, M, O孔中 (0.1μL 100% DMSO)中进行。使用 HTRF试剂盒优化PI3K 实验 。实验试剂盒中含7种试剂: 1) 4X 反应Buffer; 2) PIP2 (底物); 3) Stop A (EDTA); 4) Stop B (生物素-PIP3); 5) 检测混合物A (链霉亲和素-APC); 6)检测混合物 B (Eu-标记的抗-GST抗体和 GST标记的 PH域); 7) 检测混合物 C (KF)。通过使用去离子水按1:4稀释而制备PI3K反应 Buffer。加入新鲜制备的 DTT，终浓度为5 mM。加入酶，使用Multidrop Combi 在1X反应 buffer中加入2.5μL PI3K，加到每孔中 ，开始预温育化合物。实验板在室温下温育15分钟。 使用Multidrop Combi，加入 2.5μL 2X底物溶液(PIP2和 ATP，溶于 1X 反应buffer)开始反应。实验板在室温下温育1小时。 使用Multidrop Combi在所有孔中加入2.5μL 终止液 (Stop A和 Stop B按5:1比例预混合)，反应淬灭。使用Mulitdrop Combi(检测混合物 C, 检测混合物 A,和检测混合物 B 按18:1:1比率混合，即: 6000 μL 总体积, 混合 5400 μL 检测混合物 C, 300μL 检测混合物 A, 和 300 μL 检测混合物 B)在所有孔中加入2.5μL 检测液，进行淬火反应，检测形成的产品。备注:这种溶液在使用前2小时制备。在暗中温育1小时后，在Envision 酶标仪上测量HTRF信号，在330nm 处测定激发光，在620nm (Eu) 和665nm (APC)处双重发射光。 | ||||
| 细胞实验 | 细胞系 | BT474, HCC1954 和 T-47D | ||
| 浓度 | 0 到 1 μM | |||
| 孵育时间 | 72 小时 | |||
| 方法 | BT474, HCC1954 和 T-47D(人类乳腺)培养在含10%胎牛血清的 RPMI-1640 培养基中，培养在37oC下含 5% CO2的 孵育器中。在实验前2到3天，细胞按密度分到T75 烧瓶中，这样在实验收集时获得约70-80% 细胞汇合。使用0.25% 胰蛋白酶-EDTA收集细胞。在细胞悬液中使用台酚蓝染色排除染色，进行细胞计数。细胞按每孔1000个细胞接种在384孔黑色平底聚苯乙烯板中， 每孔含48 μL 培养基。所有实验板置于5% CO2, 37oC 下过夜，第二天加入 GSK2126458。使用CellTiter-Glo处理一个实验板，用于第一天测量。GSK2126458 在清澈见底的聚丙烯384孔板中制备，连续稀释两倍。4 μL 这些稀释液加到105 μL 培养基中混合溶液后, 细胞板的每孔中加入2 μL这些稀释液。所有孔中的 DMSO 终浓度为0.15%。细胞在37oC, 5% CO2 环境中温育 72小时。随后与 GSK2126458温育72小时。CellTiter-Glo试剂加到实验板中，使用与孔中细胞培养体积相当量的体积。震荡实验板约2分钟，在室温下温育约30分钟，然后在Analyst GT 读数器上读取化学分光信号。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-AKT / AKT / p-RPS6 / RPS6 / p-4E-BP1 / 4E-BP1 |
|
31069214 | |
| Growth inhibition assay | IC50 |
|
26148118 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | GSK2126458作用于BT474人类移植瘤模型，降低pAKT-S473水平，这种作用存在剂量依赖性，按300 μg /kg低剂量处理抑制肿瘤生长，这种作用存在剂量依赖性。此外, GSK2126458 作用于四种临床前期物种(小鼠, 大鼠,犬 ,和猴 )，具有低血液清除力和良好口服生物有效性。[1] | |
|---|---|---|
| 动物实验 | Animal Models | 在小鼠体内移植BT474肿瘤 |
| Dosages | ≤300 μg /kg | |
| Administration | 口服处理 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01725139 | Completed | Idiopathic Pulmonary Fibrosis |
GlaxoSmithKline |
March 8 2013 | Phase 1 |
| NCT01248858 | Terminated | Cancer |
GlaxoSmithKline |
December 3 2010 | Phase 1 |
| NCT00972686 | Completed | Solid Tumours |
GlaxoSmithKline |
August 31 2009 | Phase 1 |
化学信息&溶解度
| 分子量 | 505.5 | 分子式 | C25H17F2N5O3S |
| CAS号 | 1086062-66-9 | SDF | Download Omipalisib (GSK2126458) SDF |
| Smiles | COC1=C(C=C(C=N1)C2=CC3=C(C=CN=C3C=C2)C4=CN=NC=C4)NS(=O)(=O)C5=C(C=C(C=C5)F)F | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 30 mg/mL ( (59.34 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : 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）
mg/kg
g
μL
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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