Uprosertib (GSK2141795)

製品コードS7492 バッチS749202

印刷

化学情報

Chemical Structure Synonyms GSK795 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H16Cl2F2N4O2
分子量 429.25 CAS No. 1047634-65-0
Solubility (25°C)* 体外 DMSO 85 mg/mL (198.01 mM)
Ethanol 85 mg/mL (198.01 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 Uprosertib (GSK2141795, GSK795) is a selective, ATP-competitive, and orally bioavailable Akt inhibitor with IC50 of 180 nM, 328 nM, and 38 nM for Akt 1, 2 and 3, respectively. Phase 2.
in vitro Uprosertib inhibits multiple AKT substrate phosphorylation levels, including GSK3β, PRAS40, FOXO and Caspase 9 in both BT474 and LNCaP cells. Uprosertib preferentially inhibits the proliferation of human cancer cells lines with AKT pathway activation. In LNCaP, BT474, A3 and I9.2 cells lines, Uprosertib also causes cell cycle arrest. [2] In both SKOV3 and PEO4 cells, Uprosertib causes growth-arrest as single agent, and enhances cisplatin-induced apoptosis. [3]
in vivo In mice bearing BT474 breast tumor xenografts, Uprosertib (100 mg/kg, p.o.) results 61% tumor growth inhibition. In mice bearing SKOV3 ovarian tumor xenografts, Uprosertib (30 mg/kg, p.o.) results 61% tumor growth inhibition. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Selectivity profiling experiments
The lysates (5 mg of total protein each) are preincubated with 0 (DMSO control), 2.5 nM, 25 nM, 250 nM, 2.5 μM or 25 μM free compound (GSK690693 or GSK2141795) on an end-over-end shaker for 45 min at 4 °C. Subsequently, lysates are incubated with beads (coupled Akt probe or kinobeads) for 1 h at 4 °C, for both qualitative and quantitative experiments. The beads are washed with 1× CP buffer and collected by centrifugation. Bound proteins are eluted with 2× NuPAGE LDS sample buffer, and eluates are reduced and alkylated by 50 mM dithiothreitol and 55 mM iodoacetamide.
細胞アッセイ 細胞株 A panel of 290 cells lines
濃度 ~30 μM
反応時間 3 d
実験の流れ Cell lines are typically grown in RPMI 160 medium containing 10% FBS. Some cell lines are grown in media specified by the vendor. A 3-day proliferation assay using CellTiter-Glo is performed to measure the growth inhibition by the compounds at 0–30 µM. Cell growth is determined relative to untreated (DMSO) controls. EC50's are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm in the Assay Client application.
動物実験 動物モデル Mice bearing either BT474 or SKOV3 tumors
投薬量 100 mg/kg
投与方法 p.o.

カスタマーフィードバック

Data from [Data independently produced by , , The Ohio State University, 2015]

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：

MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade [ Nat Commun, 2022, 13(1):245] PubMed: 35017531
PGE2 activates EP4 in subchondral bone osteoclasts to regulate osteoarthritis [ Bone Res, 2022, 10(1):27] PubMed: 35260562
Reversal of IKZF1-induced glucocorticoid resistance by dual targeting of AKT and ERK signaling pathways [ Front Oncol, 2022, 12:905665] PubMed: 36119546
FOXO1 Alleviates Liver Ischemia-reperfusion Injury by Regulating the Th17/Treg Ratio through the AKT/Stat3/FOXO1 Pathway [ J Clin Transl Hepatol, 2022, 10(6):1138-1147] PubMed: 36381102
MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade [ Sci Adv, 2021, 7(46):eabi6439] PubMed: 34767444
Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells. [ Br J Cancer, 2020, 10.1038/s41416-020-0777-y] PubMed: 32152504
The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis. [ Cell Oncol (Dordr), 2020, 8] PubMed: 32382996
β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells [ Sci Rep, 2020, 10(1):12644] PubMed: 32724089
MSC-secreted TGF-β regulates lipopolysaccharide-stimulated macrophage M2-like polarization via the Akt/FoxO1 pathway. [ Stem Cell Res Ther, 2019, 10(1):345] PubMed: 31771622
PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. [ Toxicol Appl Pharmacol, 2019, 381:114729] PubMed: 31445927

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。

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