Ipatasertib (GDC-0068)

製品コードS2808 バッチS280806

化学情報

	Synonyms	RG7440	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₄H₃₂ClN₅O₂
	分子量	458	CAS No.	1001264-89-6
Solubility (25°C)*	体外	DMSO	92 mg/mL (200.87 mM)
		Ethanol	92 mg/mL (200.87 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

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.
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]
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]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	PC3 cells
	濃度
	反応時間	1 h
	実験の流れ	Cells were treated with various concentrations of drug.
動物実験	動物モデル	Female nude mice bearing LNCaP, PC3, KPL-4, or MCF7 tumor xenografts
	投薬量	~100 mg/kg/day
	投与方法	Orally

参考

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カスタマーフィードバック

: Data from [Data independently produced by , , Cell, 2015, 160(1-2): 161-76 ]

: Data from [Data independently produced by , , Clin Cancer Res, 2018, 78(7):1657-1671]

: Data from [Data independently produced by , , Neoplasia, 2017, 19(4):310-320]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The highly selective and oral phosphoinositide 3-kinase delta (PI3K-δ) inhibitor roginolisib induces apoptosis in mesothelioma cells and increases immune effector cell composition [ Transl Oncol, 2024, 43:101857]	PubMed: 38412661
IFN-γ decreases PD-1 in T lymphocytes from convalescent COVID-19 patients via the AKT/GSK3β signaling pathway [ Sci Rep, 2024, 14(1):5038]	PubMed: 38424104
Cholesterol biosynthesis inhibition synergizes with AKT inhibitors in triple-negative breast cancer [ bioRxiv, 2024, 10.1101/2024.01.16.575899]	PubMed: none
Stiff matrix induces exosome secretion to promote tumour growth [ Nat Cell Biol, 2023, 25(3):415-424]	PubMed: 36797475
Alternative splicing of HDAC7 regulates its interaction with 14-3-3 proteins to alter histone marks and target gene expression [ Cell Rep, 2023, 42(3):112273]	PubMed: 36933216
SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition [ NPJ Precis Oncol, 2023, 7(1):136]	PubMed: 38102334
Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis [ Front Oncol, 2023, 13:1129682]	PubMed: 37483521
Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence [ Exp Gerontol, 2023, 173:112091]	PubMed: 36657533
P2RY2-AKT activation is a therapeutically actionable consequence of XPO1 inhibition in acute myeloid leukemia [ Nat Cancer, 2022, 3(7):837-851]	PubMed: 35668193
Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC) [ J Exp Clin Cancer Res, 2022, 41(1):193]	PubMed: 35655319

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。