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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C18H17Cl2FN4OS |
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分子量 | 427.32 | CAS No. | 1047644-62-1 | |
Solubility (25°C)* | 体外 | DMSO | 85 mg/mL (198.91 mM) | |
Ethanol | 85 mg/mL (198.91 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. |
製品説明 | Afuresertib (GSK2110183) is a potent, orally bioavailable Akt inhibitor with Ki of 0.08 nM, 2 nM, and 2.6 nM for Akt1, Akt2, and Akt3, respectively. Phase 2. |
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in vitro | Afuresertib inhibits the kinase activity of the E17K AKT1 mutant protein with EC50 of 0.2 nM. Afuresertib shows a concentration-dependent effect on multiple AKT substrate phosphorylation levels, including GSK3b, PRAS40, FOXO and Caspase 9. Overall 65% of the hematological cell lines are sensitive to afuresertib (EC50 < 1 μM). Among tested solid tumor cell lines, 21% have EC50 < 1 μM in response to afuresertib.[1] |
in vivo | Mice bearing BT474 breast tumor xenografts are dosed with afuresertib (p.o.) at 10, 30 or 100 mg/kg daily which results in 8, 37 and 61% TGI, respectively. Mice bearing SKOV3 ovarian tumor xenografts are treated with 10, 30 and 100 mg/kg afuresertib which results in 23, 37 and 97% TGI, respectively.[1] |
キナーゼアッセイ | Potency (Ki*) of afuresertib | |
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The true potency (Ki*) of the inhibitor is initially determined at low enzyme concentrations (0.1 nM AKT1, 0.7 nM AKT2, and 0.2 nM AKT3) using a filter binding assay and then confirmed with progress curve analysis. In the filter binding assay, a pre-mix of enzyme plus inhibitor is incubated for 1 h and then added to a GSKα peptide (Ac-KKGGRARTSS-FAEPG-amide) and [γ33P] ATP. Reactions are terminated after 2 h and the radio labeled AKT peptide product is captured in a phospho-cellulose filter plate. Progress curve analysis utilizes continuous real-time fluorescence detection of product formation using the Sox-AKT-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2). | ||
細胞アッセイ | 細胞株 | Hematological cell lines and solid tumor cell lines |
濃度 | 30 μM | |
反応時間 | 72 h | |
実験の流れ | 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 | Female athymic nude and SCID mice bearing SKOV3 or BT474 tumors |
投薬量 | 100 mg/kg | |
投与方法 | p.o. |
Data from [Data independently produced by , , ONCOLOGY LETTERS, 2018, https://doi.org/10.3892/ol.2018.8501]
SREBP1 deficiency diminishes glutamate-mediated HT22 cell damage and hippocampal neuronal pyroptosis induced by status epilepticus [ Heliyon, 2024, 10(1):e23945] | PubMed: 38205297 |
TLR7/8 stress response drives histiocytosis in SLC29A3 disorders [ J Exp Med, 2023, 220(9)e20230054] | PubMed: 37462944 |
Crosstalk with lung fibroblasts shapes the growth and therapeutic response of mesothelioma cells [ Cell Death Dis, 2023, 10.1038/s41419-023-06240-x] | PubMed: 37938546 |
Azeliragon inhibits PAK1 and enhances the therapeutic efficacy of AKT inhibitors in pancreatic cancer [ Eur J Pharmacol, 2023, 948:175703] | PubMed: 37028543 |
Biochemie der Myelomzelle bei Argininmangel und Canavanin-Supplementation [ DNB, 2023, ] | PubMed: none |
AKT constitutes a signal-promoted alternative exon-junction complex that regulates nonsense-mediated mRNA decay [ Mol Cell, 2022, S1097-2765(22)00480-4] | PubMed: 35675814 |
PDGF-D-PDGFRβ signaling enhances IL-15-mediated human natural killer cell survival [ Proc Natl Acad Sci U S A, 2022, 119(3)e2114134119] | PubMed: 35027451 |
Combined treatment with anti-PSMA CAR NK-92 cell and anti-PD-L1 monoclonal antibody enhances the antitumour efficacy against castration-resistant prostate cancer [ Clin Transl Med, 2022, 12(6):e901] | PubMed: 35696531 |
Focal adhesion kinase plays a dual role in TRAIL resistance and metastatic outgrowth of malignant melanoma [ Cell Death Dis, 2022, 13(1):54] | PubMed: 35022419 |
Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer [ Oncogene, 2022, 41(36):4211-4230] | PubMed: 35896617 |
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。