Ipatasertib (GDC-0068)
别名: RG7440
Ipatasertib (GDC-0068, RG7440)是一种高选择性的pan-Akt抑制剂，靶向作用于Akt1/2/3，在无细胞试验中IC50为5 nM/18 nM/8 nM，比作用于PKA选择性高620倍。Phase 2。
Ipatasertib (GDC-0068) Chemical Structure
CAS: 1001264-89-6
产品质控
批次：
纯度：
99.87%
99.87
常与Ipatasertib (GDC-0068)一起在实验中被使用的化合物
Ipatasertiba与Paclitaxel联用具有更强的降低HEC-1A和ECC-1细胞中Bcl-xL表达的能力。
Ipatasertib和Palbociclib组合使用在患者来源的肿瘤异种移植模型TMA-027中显示出显着延迟的肿瘤生长。
Kase AM, et al. Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022) 176-176.
Ipatasertib和Carboplatin联合使用可显着抑制ARK-1和SPEC-2细胞中的细胞增殖并降低Bcl-XL和MCL-1的表达。
Ipatasertib和Erdafitinib联合治疗可协同抑制细胞增殖并诱导膀胱癌(BC)细胞死亡。
Hu C, et al. Biochem Biophys Res Commun. 2022 May 14;604:165-171.
Ipatasertib和Bevacizumab联合使用可减少子宫内膜样子宫内膜癌(EC)转基因小鼠模型中的肿瘤生长。
Ipatasertib (GDC-0068)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 |
|---|---|---|---|---|---|
| PC-3 | Growth Inhibition Assay | 1/5/10 μM | 24/48/72 h | dose-dependently increases the G0–G1 phase population | 23287563 |
| IGROV-1 | Function Assay | 0.0038-2.5 μM | 1 h | induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473 | 23287563 |
| BT474M1 | Function Assay | 0.0038-2.5 μM | 1 h | induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473 | 23287563 |
| PC-3 | Function Assay | 0.0038-2.5 μM | 1 h | induces a dose-dependent increase in Akt phosphorylation at both Thr308 (T308) and Ser473 | 23287563 |
| MDA-MB-468 | Growth Inhibition Assay | 1 μM | 5 d | enhances the antiproliferative response | 24667376 |
| HCC70 | Growth Inhibition Assay | 1 μM | 5 d | enhances the antiproliferative response | 24667376 |
| MDA-MB-468 | Function Assay | 1 μM | 24 h | increases the abundance of HER3 | 24667376 |
| HCC70 | Function Assay | 1 μM | 24 h | increases the abundance of HER3 and induces the phosphorylation (activation) of both EGFR and HER3 | 24667376 |
| MCF7-neo/HER2 | Growth Inhibition Assay | 1/5/10 μM | 24/48/72 h | dose-dependently increases the G0–G1 phase population | 23287563 |
| BT474M1 | Growth Inhibition Assay | 1/5/10 μM | 24/48/72 h | dose-dependently increases the G0–G1 phase population | 23287563 |
| PC-3 | Apoptosis Assay | 1/5/10 μM | 15/48/72 h | causes a dose- and time-dependent increase in apoptotic and necrotic populations | 23287563 |
| MCF7-neo/HER2 | Apoptosis Assay | 1/5/10 μM | 15/48/72 h | causes a dose- and time-dependent increase in apoptotic and necrotic populations | 23287563 |
| BT474M1 | Apoptosis Assay | 1/5/10 μM | 15/48/72 h | causes a dose- and time-dependent increase in apoptotic and necrotic populations | 23287563 |
| PC3 | Function assay | 50 mg/kg | 9 hrs | Plasma concentration in nu/nu mouse xenografted with human PC3 cells at 50 mg/kg, po at 9 hrs by LC/MS/MS analysis, Cp = 0.5 μM. | 22934575 |
| PC3 | Function assay | 50 mg/kg | 1 hr | Plasma concentration in nu/nu mouse xenografted with human PC3 cells at 50 mg/kg, po at 1 hr by LC/MS/MS analysis, Cp = 7.4 μM. | 22934575 |
| PC3 | Function assay | 100 mg/kg | 8 hrs | Inhibition of Akt in nu/nu mouse xenografted with human PC3 cells assessed as decrease in tumor p-S6RP level at 100 mg/kg, po at 8 hrs by ELISA relative to total S6RP | 22934575 |
| LNCAP | Cytotoxicity assay | 72 hrs | Cytotoxicity against human LNCAP cells assessed as reduction of resazurin to resorufin after 72 hrs, IC50 = 0.095 μM. | 22934575 | |
| LNCAP | Function assay | 1.5 hrs | Inhibition of Akt1 in human LNCAP cells assessed as phosphorylation of PRAS40 at Thr246 after 1.5 hrs, IC50 = 0.157 μM. | 22934575 | |
| BT474M1 | Cytotoxicity assay | 96 hrs | Cytotoxicity against human BT474M1 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM. | 22934575 | |
| PC3 | Cytotoxicity assay | 96 hrs | Cytotoxicity against human PC3 cells assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM. | 22934575 | |
| MCF7 | Cytotoxicity assay | 96 hrs | Cytotoxicity against human MCF7 cells overexpressing Her2 assessed as decrease in cell viability after 96 hrs by CellTitre-Glo assay, IC50 = 1 μM. | 22934575 | |
| MCF7 | Function assay | Inhibition of Akt1-mediated PRAS40 phosphorylation in human MCF7 cells overexpressing Her2 | 22934575 | ||
| BT474M1 | Function assay | Inhibition of Akt1-mediated PRAS40 phosphorylation in human BT474M1 cells | 22934575 | ||
| PC3 | Function assay | Inhibition of Akt1-mediated PRAS40 phosphorylation in human PC3 cells | 22934575 | ||
| LNCAP | Function assay | Inhibition of Akt1-mediated PRAS40 phosphorylation in human LNCAP cells | 22934575 | ||
| 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 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) 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 | ||
| 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 | ||
| 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: Confirmatory screen for Rh30 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 | ||
| 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 | ||
| 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 | Ipatasertib (GDC-0068, RG7440)是一种高选择性的pan-Akt抑制剂，靶向作用于Akt1/2/3，在无细胞试验中IC50为5 nM/18 nM/8 nM，比作用于PKA选择性高620倍。Phase 2。 | ||||||
|---|---|---|---|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | 对一大组230种激酶测试，GDC-0068只抑制3种激酶，浓度为 1 μM 时抑制70%以上,(抑制PRKG1α,PRKG1β,和p70S6K时, IC50分别为98 nM, 69 nM, 和 860 nM)。GDC-0068 作用于Akt比作用于PKA 选择性高100倍以上，抑制Akt时 IC50为3.1 μM。GDC-0068处理LNCaP, PC3 和 BT474M1 细胞,抑制Akt底物PRAS40磷酸化,IC50分别为157 nM, 197 nM, 和208 nM。而且, GDC-0068选择性抑制细胞周期进展和Akt信号驱动的癌细胞活力, 包括肿瘤抑制基因PTEN缺陷,PIK3CA致癌基因突变, 和HER2扩增,在HER2+和Luminal 亚型中作用效果最强。[1-4] |
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|---|---|---|---|---|
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | PUMA p-AKT / AKT / p-FoxO3a / FoxO3a / p-p65 / p65 Noxa / Bid / Bad / Bim / Bcl-2 / Bcl-xl / Mcl-1 cleaved-caspase3 p-PRAS40(T246) / PRAS40 / p-ERK / ERK / pFOXO1 / pFOXO3a / pGSK3b(S9) / pAS160(S318) / pBAD(S136) / pS6 / p4E-BP1 |
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30185800 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | GDC-0068口服处理给药PC3前列腺移植瘤模型，诱导p-PRAS40下调。GDC-0068 处理BT474-Tr移植瘤,降低 pS6 和 peIF4G 水平,重新定位FOXO3a到细胞核,且诱导 HER3 和pERK的反馈上调。GDC-0068 处理多种移植瘤模型，具有有效抗癌活性，包括PTEN-缺陷的前列腺癌模型LNCaP 和 PC3, PIK3CA H1047R 突变的乳腺癌模型 KPL-4, 和 MCF7-neo/HER2肿瘤模型。[1-4] |
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|---|---|---|
| 动物实验 | Animal Models | 携带LNCaP, PC3, KPL-4, 或MCF7移植瘤的雌性裸鼠 |
| Dosages | ~100 mg/kg/day | |
| Administration | 口服处理 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01090960 | Completed | Solid Cancers |
Genentech Inc. |
March 2010 | Phase 1 |
化学信息&溶解度
| 分子量 | 458 | 分子式 | C24H32ClN5O2 |
| CAS号 | 1001264-89-6 | SDF | Download Ipatasertib (GDC-0068) SDF |
| Smiles | CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 91 mg/mL ( (198.68 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 91 mg/mL (198.68 mM) 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）
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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