Ipatasertib (GDC-0068)

製品コードS2808 バッチS280803

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

+ 展开

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：

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution [ Nature, 2024, 10.1038/s41586-024-08031-6]	PubMed: 39385030
Arachidonic acid released by PIK3CA mutant tumor cells triggers malignant transformation of colonic epithelium by inducing chromatin remodeling [ Cell Rep Med, 2024, S2666-3791(24)00179-4]	PubMed: 38614093
Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer [ Cancer Lett, 2024, 604:217219]	PubMed: 39244005
Assessments of prostate cancer cell functions highlight differences between a pan-PI3K/mTOR inhibitor, gedatolisib, and single-node inhibitors of the PI3K/AKT/mTOR pathway [ Mol Oncol, 2024, 10.1002/1878-0261.13703]	PubMed: 39092562
Down-Regulation of AKT Proteins Slows the Growth of Mutant-KRAS Pancreatic Tumors [ Cells, 2024, 13(12)1061]	PubMed: 38920688
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
Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors [ bioRxiv, 2024, 2024.05.03.592345]	PubMed: 38746217
Cholesterol biosynthesis inhibition synergizes with AKT inhibitors in triple-negative breast cancer [ bioRxiv, 2024, 10.1101/2024.01.16.575899]	PubMed: none
Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors [ bioRxiv, 2024, 2024.04.02.587656]	PubMed: 38617302

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。