Ipatasertib (GDC-0068)

Ipatasertib (GDC-0068, RG7440) is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM in cell-free assays, 620-fold selectivity over PKA. Phase 2.

CAS No. 1001264-89-6

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 56700	国内在庫あり
5mg	JPY 40500	国内在庫あり
25mg	JPY 118500	国内在庫あり
100mg	JPY 250500	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（114）

製品安全説明書

現在のバッチを見る：純度： 99.87%

99.87

Ipatasertib (GDC-0068)と併用されることが多い化合物

Paclitaxel

Ipatasertiba and Paclitaxel combination has a greater ability to reduce the expression of Bcl-xL in HEC-1A and ECC-1 cells.

O'Donnell J, et al. Int J Oncol. 2023 Sep;63(3):103.

Palbociclib

Ipatasertib and Palbociclib combination use displays significantly delayed tumor growth in a patient-derived tumor xenograft model, TMA-027.

Kase AM, et al. Journal of Clinical Oncology 40, no. 6_suppl (February 20, 2022) 176-176.

Carboplatin

Ipatasertib and Carboplatin combination use significantly inhibits cell proliferation and reduces expression of both Bcl-XL and MCL-1 in ARK-1 and SPEC-2 cells.

Burkett WC, et al. Ann Med. 2023 Dec;55(1):603-614.

Erdafitinib

Ipatasertib and Erdafitinib co-treatment synergistically inhibits cell proliferation and induces bladder cancer (BC) cell death.

Hu C, et al. Biochem Biophys Res Commun. 2022 May 14;604:165-171.

Bevacizumab (anti-VEGF)

Ipatasertib and Bevacizumab combination use reduces tumor growth in a transgenic mouse model of endometrioid endometrial cancers (ECs).

Newton M, et al. Gynecologic Oncology 166 (2022): S31.

Ipatasertib (GDC-0068)関連製品

関連ターゲット	Akt1 Akt2 Akt3	もっと見る
関連製品	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) Miransertib (ARQ 092) HCl Miltefosine AT13148 Uprosertib (GSK2141795) Miransertib (ARQ-092) SC66 Deguelin ML-9 HCl	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

Aktシグナル伝達経路

Akt阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	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
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生物活性

製品説明

Ipatasertib (GDC-0068, RG7440) is a highly selective pan-Akt inhibitor targeting Akt1/2/3 with IC50 of 5 nM/18 nM/8 nM in cell-free assays, 620-fold selectivity over PKA. Phase 2.

Targets

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

In Vitro
In vitro	Testing against a broad panel of 230 kinases, GDC-0068 only inhibits 3 kinases by >70% at 1 μM concentration (PRKG1α, PRKG1β, and p70S6K, with IC50 of 98 nM, 69 nM, and 860 nM, respectively). GDC-0068 displays >100-fold selectivity for Akt over PKA with IC50 of 3.1 μM. In LNCaP, PC3 and BT474M1 cells, GDC-0068 treatment inhibits the phosphorylation of the Akt substrate, PRAS40 with IC50 of 157 nM, 197 nM, and 208 nM, respectively. Furthermore, GDC-0068 selectively inhibits cell cycle progression and viability of cancer cell lines driven by Akt signaling, including those with defects in the tumor suppressor PTEN, oncogenic mutations in PIK3CA, and amplification of HER2, with strongest effects in HER2⁺ and Luminal subtypes. ^[1-4]
実験結果図	Methods	Biomarkers	結果図	PMID
実験結果図	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

In Vivo
In Vivo	Oral administration of GDC-0068 in PC3 prostate tumor xenografts model induces down-regulation of p-PRAS40. In BT474-Tr xenografts, GDC-0068 treatment reduces pS6 and peIF4G levels, re-localizes FOXO3a to nucleus, and induces feedback upregulation of HER3 and pERK. Administration of GDC-0068 exhibits potent antitumor efficacy in multiple xenograft tumor models, including the PTEN-deficient prostate cancer models LNCaP and PC3, the PIK3CA H1047R mutant breast cancer model KPL-4, and MCF7-neo/HER2 tumor model. ^[1-4]
動物実験	動物モデル	Female nude mice bearing LNCaP, PC3, KPL-4, or MCF7 tumor xenografts
	投与量	~100 mg/kg/day
	投与経路	Orally

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT01090960	Completed	Solid Cancers	Genentech Inc.	March 2010	Phase 1

参考
[1] Lin K. Cancer Res, 2011, 71(8 Supplement), abstract DDT02-01. [2] James F. Blake. 2011. [3] Tabernero J, et al. Ann Oncol, 2011, 22(suppl 3), abstract IL33. [4] Heidi M. Savage, et al. Cancer Res, 2012, 72(8 Supplement), 966. [5] Roel Funke, et al. American Society of Clinical Oncology (ASCO) Annual Meeting, 1-5, 2012. [6] Lin J, et al. Clin Cancer Res. 2013 Apr 1;19(7):1760-72. + 展開

参考

+ 展開

化学情報

分子量	458	化学式	C₂₄H₃₂ClN₅O₂
CAS No.	1001264-89-6	SDF	Download Ipatasertib (GDC-0068) SDFをダウンロードする
Smiles	CC1CC(C2=C1C(=NC=N2)N3CCN(CC3)C(=O)C(CNC(C)C)C4=CC=C(C=C4)Cl)O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 91 mg/mL ( (198.68 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 91 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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):