Afuresertib (GSK2110183)

製品コードS7521 バッチS752101

印刷

化学情報

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

C18H17Cl2FN4OS
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
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 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.
in vitro Afuresertib (GSK2110183) inhibits the kinase activity of the E17K AKT1 mutant protein with an EC50 of 0.2 nM. It 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 this compound (EC50 < 1 μM). Among tested solid tumor cell lines, 21% have EC50 < 1 μM in response to afuresertib.
in vivo Afuresertib (GSK2110183) was administered orally at 10, 30 or 100 mg/kg daily to mice bearing BT474 breast tumor xenografts, resulting in 8, 37 and 61% TGI, respectively. In mice bearing SKOV3 ovarian tumor xenografts, treatment with 10, 30 and 100 mg/kg of this compound resulted in 23, 37 and 97% TGI, respectively.

プロトコル(参考用のみ)

キナーゼアッセイ Potency (Ki*) of afuresertib
The true potency (Ki*) of Afuresertib (GSK2110183) 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 this compound 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 Afuresertib (GSK2110183) is evaluated using a 3-day proliferation assay with CellTiter-Glo to measure its growth inhibition 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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/24978597/

カスタマーフィードバック

Data from [Data independently produced by , , ONCOLOGY LETTERS, 2018, https://doi.org/10.3892/ol.2018.8501]

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：

Starvation-induced phosphorylation activates gasdermin A to initiate pyroptosis [ Cell Rep, 2024, 43(9):114728] PubMed: 39264808
p53 modulates kinase inhibitor resistance and lineage plasticity in NF1-related MPNSTs [ Oncogene, 2024, 43(19):1411-1430] PubMed: 38480916
Interleukin-2-mediated NF-κB-dependent mRNA splicing modulates interferon gamma protein production [ EMBO Rep, 2024, 10.1038/s44319-024-00324-1] PubMed: 39578552
Viral microRNA regulation of Akt is necessary for reactivation of Human Cytomegalovirus from latency in CD34+ hematopoietic progenitor cells and humanized mice [ PLoS Pathog, 2024, 20(12):e1012285] PubMed: 39661658
GRHL2-HER3 and E-cadherin mediate EGFR-bypass drug resistance in lung cancer cells [ Front Cell Dev Biol, 2024, 12:1511190] PubMed: 39897079
SREBP1 deficiency diminishes glutamate-mediated HT22 cell damage and hippocampal neuronal pyroptosis induced by status epilepticus [ Heliyon, 2024, 10(1):e23945] PubMed: 38205297
Primary Central Nervous System Lymphoma Tumor Biopsies Show Heterogeneity in Gene Expression Profiles, Genetic Subtypes, and in vitro Drug Sensitivity to Kinase Inhibitors [ medRxiv, 2024, 2024.11.11.24316310] PubMed: 39677423
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

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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