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Omipalisib (GSK2126458)
僅限科研使用
Omipalisib (GSK2126458)
別名: GSK458
Omipalisib (GSK2126458, GSK458)是一種高選擇性的，有效的p110α/β/γ/δ和 mTORC1/2抑制劑，無細(xì)胞試驗(yàn)中Ki分別為0.019 nM/0.13 nM/0.024 nM/0.06 nM和0.18 nM/0.3 nM。Omipalisib 可誘導(dǎo)自噬。Phase 1。
Omipalisib (GSK2126458) Chemical Structure
CAS: 1086062-66-9
產(chǎn)品質(zhì)控
批次：
純度：
99.46%
99.46
Omipalisib (GSK2126458)相關(guān)產(chǎn)品
相關(guān)信號(hào)通路圖
細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例
| 細(xì)胞系 | 實(shí)驗(yàn)類型 | 給藥濃度 | 孵育時(shí)間 | 活性描述 | 文獻(xiàn)信息(PMID) |
|---|---|---|---|---|---|
| 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 | ||
| 點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù) | |||||
生物活性
| 產(chǎn)品描述 | Omipalisib (GSK2126458, GSK458)是一種高選擇性的，有效的p110α/β/γ/δ和 mTORC1/2抑制劑，無細(xì)胞試驗(yàn)中Ki分別為0.019 nM/0.13 nM/0.024 nM/0.06 nM和0.18 nM/0.3 nM。Omipalisib 可誘導(dǎo)自噬。Phase 1。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 靶點(diǎn) |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | GSK2126458有效抑制人類癌細(xì)胞中發(fā)現(xiàn)的p110α(E542K, E545K, 和H1047R)常見激活突變型，Ki 分別為 8 pM, 8 pM 和 9 pM。GSK2126458作用于T47D和BT474 細(xì)胞，顯著降低pAKT-S473水平，IC50分別為 0.41 nM 和 0.18 nM。 而且, GSK2126458作用于多種細(xì)胞系，包括T47D 和 BT474乳腺癌細(xì)胞系，導(dǎo)致細(xì)胞周期停在G1期，且抑制細(xì)胞增殖，IC50分別為3 nM 和2.4 nM。[1] | |||
|---|---|---|---|---|
| 激酶實(shí)驗(yàn) | 體外均相時(shí)間分辨熒光技術(shù)（HTRF）測定 PI3K 抑制 | |||
| 在384孔聚丙烯母板上，化合物 (3倍溶于100% DMSO) 從1列到12列，和13列到24列連續(xù)稀釋，獲得11種濃度 GSK2126458。6列和18列只含DMSO。滴定后，0.05μL 立即轉(zhuǎn)移到384孔低容量實(shí)驗(yàn)板上。 實(shí)驗(yàn)板中含3種藥物對(duì)照(PI3K 抑制劑)和3組實(shí)驗(yàn)對(duì)照: (1) 不含抑制劑的酶實(shí)驗(yàn);(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 反應(yīng) buffer (1μL 200 μM PIP3)中， 交替 18列的行數(shù) ( B, D, F, H, J, L, N, P)。不含酶的對(duì)照實(shí)驗(yàn)在 A, C, E, G, I, K, M, O孔中 (0.1μL 100% DMSO)中進(jìn)行。使用 HTRF試劑盒優(yōu)化PI3K 實(shí)驗(yàn) 。實(shí)驗(yàn)試劑盒中含7種試劑: 1) 4X 反應(yīng)Buffer; 2) PIP2 (底物); 3) Stop A (EDTA); 4) Stop B (生物素-PIP3); 5) 檢測混合物A (鏈霉親和素-APC); 6)檢測混合物 B (Eu-標(biāo)記的抗-GST抗體和 GST標(biāo)記的 PH域); 7) 檢測混合物 C (KF)。通過使用去離子水按1:4稀釋而制備PI3K反應(yīng) Buffer。加入新鮮制備的 DTT，終濃度為5 mM。加入酶，使用Multidrop Combi 在1X反應(yīng) buffer中加入2.5μL PI3K，加到每孔中 ，開始預(yù)溫育化合物。實(shí)驗(yàn)板在室溫下溫育15分鐘。 使用Multidrop Combi，加入 2.5μL 2X底物溶液(PIP2和 ATP，溶于 1X 反應(yīng)buffer)開始反應(yīng)。實(shí)驗(yàn)板在室溫下溫育1小時(shí)。 使用Multidrop Combi在所有孔中加入2.5μL 終止液 (Stop A和 Stop B按5:1比例預(yù)混合)，反應(yīng)淬滅。使用Mulitdrop Combi(檢測混合物 C, 檢測混合物 A,和檢測混合物 B 按18:1:1比率混合，即: 6000 μL 總體積, 混合 5400 μL 檢測混合物 C, 300μL 檢測混合物 A, 和 300 μL 檢測混合物 B)在所有孔中加入2.5μL 檢測液，進(jìn)行淬火反應(yīng)，檢測形成的產(chǎn)品。備注:這種溶液在使用前2小時(shí)制備。在暗中溫育1小時(shí)后，在Envision 酶標(biāo)儀上測量HTRF信號(hào)，在330nm 處測定激發(fā)光，在620nm (Eu) 和665nm (APC)處雙重發(fā)射光。 | ||||
| 細(xì)胞實(shí)驗(yàn) | 細(xì)胞系 | BT474, HCC1954 和 T-47D | ||
| 濃度 | 0 到 1 μM | |||
| 孵育時(shí)間 | 72 小時(shí) | |||
| 方法 | BT474, HCC1954 和 T-47D(人類乳腺)培養(yǎng)在含10%胎牛血清的 RPMI-1640 培養(yǎng)基中，培養(yǎng)在37oC下含 5% CO2的 孵育器中。在實(shí)驗(yàn)前2到3天，細(xì)胞按密度分到T75 燒瓶中，這樣在實(shí)驗(yàn)收集時(shí)獲得約70-80% 細(xì)胞匯合。使用0.25% 胰蛋白酶-EDTA收集細(xì)胞。在細(xì)胞懸液中使用臺(tái)酚藍(lán)染色排除染色，進(jìn)行細(xì)胞計(jì)數(shù)。細(xì)胞按每孔1000個(gè)細(xì)胞接種在384孔黑色平底聚苯乙烯板中， 每孔含48 μL 培養(yǎng)基。所有實(shí)驗(yàn)板置于5% CO2, 37oC 下過夜，第二天加入 GSK2126458。使用CellTiter-Glo處理一個(gè)實(shí)驗(yàn)板，用于第一天測量。GSK2126458 在清澈見底的聚丙烯384孔板中制備，連續(xù)稀釋兩倍。4 μL 這些稀釋液加到105 μL 培養(yǎng)基中混合溶液后, 細(xì)胞板的每孔中加入2 μL這些稀釋液。所有孔中的 DMSO 終濃度為0.15%。細(xì)胞在37oC, 5% CO2 環(huán)境中溫育 72小時(shí)。隨后與 GSK2126458溫育72小時(shí)。CellTiter-Glo試劑加到實(shí)驗(yàn)板中，使用與孔中細(xì)胞培養(yǎng)體積相當(dāng)量的體積。震蕩實(shí)驗(yàn)板約2分鐘，在室溫下溫育約30分鐘，然后在Analyst GT 讀數(shù)器上讀取化學(xué)分光信號(hào)。 | |||
| 實(shí)驗(yàn)圖片 | 檢測方法 | 檢測指標(biāo) | 實(shí)驗(yàn)圖片 | PMID |
| Western blot | p-AKT / AKT / p-RPS6 / RPS6 / p-4E-BP1 / 4E-BP1 |
|
31069214 | |
| Growth inhibition assay | IC50 |
|
26148118 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | GSK2126458作用于BT474人類移植瘤模型，降低pAKT-S473水平，這種作用存在劑量依賴性，按300 μg /kg低劑量處理抑制腫瘤生長，這種作用存在劑量依賴性。此外, GSK2126458 作用于四種臨床前期物種(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] | |
|---|---|---|
| 動(dòng)物實(shí)驗(yàn) | Animal Models | 在小鼠體內(nèi)移植BT474腫瘤 |
| Dosages | ≤300 μg /kg | |
| Administration | 口服處理 | |
| 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 |
|
化學(xué)信息&溶解度
| 分子量 | 505.5 | 分子式 | C25H17F2N5O3S |
| CAS號(hào) | 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 | ||
| 儲(chǔ)存條件(自收到貨起) | |||
|
體外溶解度 |
DMSO : 30 mg/mL ( (59.34 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO) Water : Insoluble Ethanol : Insoluble |
摩爾濃度計(jì)算器 |
|
體內(nèi)溶解配方 現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動(dòng)物體內(nèi)配方計(jì)算器 | |||||
實(shí)驗(yàn)計(jì)算
摩爾濃度計(jì)算器
動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）
第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過程中的損耗，建議多配一只動(dòng)物的藥量）
mg/kg
g
μL
只
第二步：請(qǐng)輸入動(dòng)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(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計(jì)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(qǐng)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(jìn)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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