Miransertib (ARQ 092) HCl

製品コードS8339 バッチS833902

印刷

化学情報

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

C27H25ClN6
分子量 468.98 CAS No. 1313883-00-9
Solubility (25°C)* 体外 DMSO 75 mg/mL (159.92 mM)
Ethanol 4 mg/mL (8.52 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5% DMSO 95% Corn oil
0.31mg/ml Taking the 1 mL working solution as an example, add 50 μL of 6.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
1.25mg/ml Taking the 1 mL working solution as an example, add 50 μL of 25 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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 Miransertib (ARQ 092) HCl is a novel, orally bioavailable and selective AKT pathway inhibitor exhibiting a manageable safety profile among patients with advanced solid tumors.
in vitro ARQ 092 blocks membrane translocation of inactive AKT and even dephosphorylates the membrane-associated active form, thereby perturbing AKT activity. Treatment with 50-500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets[2]. In a large panel of diverse cancer cell lines, ARQ 092 inhibits proliferation across multiple tumor types but are most potent in leukemia, breast, endometrial, and colorectal cancer cell lines. Moreover, inhibition by ARQ 092 is more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations[1]. ARQ 092 targets the PI3K/AKT pathway and AKT specifically and reduces phosphorylation of GSK3α and GSK3β in mutation-positive cells[3].
in vivo Short-term oral administration of ARQ 092 or hydroxyurea, a main therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with TNF-α. ARQ 092 is well tolerated at a continuous daily dose of 60 mg or a dose of 600 mg when administered once a week, for several months. ARQ 092 is likely to inhibit the activity of all AKT isoforms in intravascular cells and thereby attenuates the process of thrombosis and inflammation in SCD patients[2]. ARQ 092 is highly active in a subset of endometrial tumors that harbor PI3K pathway gene mutations[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MDA-MB-453 cells; NCI-H1650 cells; KU-19-19 cells
濃度 0, 0.012, 0.037, 0.11, 0.33, and 1 μM
反応時間 2 h
実験の流れ Cells (MDA-MB-453: 1.5×106; NCI-H1650: 1×106; KU-19-19: 0.7×106) are plated into 6 well plates, left overnight, and then treated with full media containing different concentrations (0, 0.012, 0.037, 0.11, 0.33, and 1 μM) of AKT inhibitors (ARQ 092, ARQ 751, MK-2206, GDC-0068) for 2 hours. Cells are treated under designated conditions and lysates are extracted. Proteins are resolved from extracts using SDS-PAGE followed by immunoblotting.
動物実験 動物モデル Male SCD mice
投薬量 100 mg/10ml/kg
投与方法 oral administration

カスタマーフィードバック

Data from [Data independently produced by , , Neurobiol Dis, 2018, pii: S0969-9961(18)30149-9]

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：

Insights into the Conformational Plasticity of the Protein Kinase Akt1 by Multi-Lateral Dipolar Spectroscopy [ Chemistry, 2023, e202203959.] PubMed: 36795969
AKT mutant allele-specific activation dictates pharmacologic sensitivities [ Nat Commun, 2022, 13(1):2111] PubMed: 35440569
Cilia-Mediated Insulin/Akt and ST2/JNK Signaling Pathways Regulate the Recovery of Muscle Injury [ Adv Sci (Weinh), 2022, e2202632] PubMed: 36373718
Revisiting the Resazurin-Based Sensing of Cellular Viability: Widening the Application Horizon [ Biosensors (Basel), 2022, 12(4)196] PubMed: 35448256
Viability fingerprint of glioblastoma cell lines: roles of mitotic, proliferative, and epigenetic targets [ Sci Rep, 2021, 11(1):20338] PubMed: 34645858
1,3-dichloro-2-propanol induced hepatic lipid accumulation by inhibiting autophagy via AKT/mTOR/FOXO1 pathway in mice [ Food Chem Toxicol, 2021, 157:112578] PubMed: 34560177
Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury [ Int J Biol Sci, 2020, 16(14):2559-2579] PubMed: 32792857
FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti [ Dev Dyn, 2020, 10.1002/dvdy.231] PubMed: 32735383
Preclinical Efficacy of Covalent-Allosteric AKT Inhibitor Borussertib in Combination with Trametinib in KRAS-Mutant Pancreatic and Colorectal Cancer. [ Cancer Res, 2019, 79(9):2367-2378] PubMed: 30858154
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。

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。