Ipatasertib (GDC-0068)

别名: RG7440

目录号：S2808 Purity: 99.87%

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

规格	价格	库存
10mM (1mL in DMSO)	1392.3	现货
5mg	1203.93	现货
25mg	3595.41	现货
50mg	5708.43	现货
100mg	9148.23	现货
更大包装有超大折扣
400-668-6834 info@selleck.cn

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

Paclitaxel

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。

Palbociclib

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。

Carboplatin

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。

Erdafitinib

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。

Bevacizumab (anti-VEGF)

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

相关靶点	Akt1 Akt2 Akt3	点击展开
相关产品	MK-2206 2HCl Perifosine SC79 Capivasertib (AZD5363) GSK690693 Triciribine (API-2) CCT128930 Afuresertib (GSK2110183) A-674563 HCl AT7867 Oridonin Akti-1/2 PHT-427 TIC10 (ONC201) AT13148 Miransertib (ARQ 092) HCl Uprosertib (GSK2141795) 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	给药浓度	孵育时间	活性描述	文献信息(PMID)
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

Akt1 ^[1] (Cell-free assay)	Akt3 ^[1] (Cell-free assay)	Akt2 ^[1] (Cell-free assay)
5 nM	8 nM	18 nM

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]
实验图片	检测方法	检测指标	实验图片	PMID
实验图片	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		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]
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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT01090960	Completed	Solid Cancers	Genentech Inc.	March 2010	Phase 1

参考文献
http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/71/8_MeetingAbstracts/DDT02-01?sid=e2 http://www.arraybiopharma.com/_documents/Publication/PubAttachment478.pdf http://www.arraybiopharma.com/_documents/Publication/PubAttachment437.pdf http://cancerres.aacrjournals.org/cgi/content/short/72/8_MeetingAbstracts/966?rss=1 http://www.arraybiopharma.com/_documents/Publication/PubAttachment524.pdf https://pubmed.ncbi.nlm.nih.gov/23287563/ + 展开

参考文献

http://cancerres.aacrjournals.org/cgi/content/meeting_abstract/71/8_MeetingAbstracts/DDT02-01?sid=e2
http://www.arraybiopharma.com/_documents/Publication/PubAttachment478.pdf
http://www.arraybiopharma.com/_documents/Publication/PubAttachment437.pdf

http://cancerres.aacrjournals.org/cgi/content/short/72/8_MeetingAbstracts/966?rss=1
http://www.arraybiopharma.com/_documents/Publication/PubAttachment524.pdf
https://pubmed.ncbi.nlm.nih.gov/23287563/

+ 展开

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)	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 : 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

DMSO : 92 mg/mL ( (200.87 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 92 mg/mL (200.87 mM)

Water : 10 mg/mL (21.83 mM)

DMSO : 92 mg/mL ( (200.87 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 92 mg/mL (200.87 mM)

Water : Insoluble

DMSO : 92 mg/mL ( (200.87 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 92 mg/mL (200.87 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解配方批次：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
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
澄清溶液	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	4.600mg/ml (10.04mM)	以 1 mL 工作液为例，取50μL92mg/ml的澄清DMSO储备液加到400μL PEG300中，混合均匀使其澄清；向上述体系中加入50μLTween80，混合均匀使其澄清；然后继续加入500μL ddH2O定容至 1 mL。工作液请现配现用！
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。

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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操作手册

如果有其他问题，请给我们留言。

* 必填项

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Ipatasertib (GDC-0068)

产品质控

常与Ipatasertib (GDC-0068)一起在实验中被使用的化合物

Ipatasertib (GDC-0068)相关产品

相关信号通路图

细胞实验数据示例

生物活性

化学信息&溶解度

实验计算

技术支持