VX-11e

製品コードS7709 バッチS770901

印刷

化学情報

Chemical Structure Synonyms VTX-11e, Vertex-11e Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H20Cl2FN5O2
分子量 500.35 CAS No. 896720-20-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (199.86 mM)
Ethanol 16 mg/mL (31.97 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.
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (9.99mM) Taking the 1 mL working solution as an example, add 50 μL of 100 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 make it clear; 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 VX-11e (VTX-11e, Vertex-11e) is a potent, selective, and orally bioavailable ERK inhibitor with IC50 of 17 nM (ERK1) and 15 nM (ERK2), over 200-fold selective over other kinases tested.
in vitro In HT29 cells, VX-11e potently inhibits cell proliferation with IC50 of 48 nM. [1]
in vivo In both rats and mice, VX-11e shows good oral bioavailability. [1] In NSG mice bearing human melanoma RPDX tumors, this compound (50 mg/kg, p.o.) results in robust inhibition of pRSK, and inhibits tumor growth. When used in combination with BKM120, this chemical results in significantly improved tumor growth inhibition. [2]

プロトコル(参考用のみ)

キナーゼアッセイ ERK Inhibition Assay
Compounds are assayed for the inhibition of ERK2 by a spectophotometric coupled-enzyme assay. In this assay, a fixed concentration of activated ERK2 (10 nM) is incubated with various concentrations of the compounds in DMSO (2.5%) for 10 min. at 30 °C in 0.1 M HEPES buffer, pH = 7.5, containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 μM NADH, 150 μg/mL pyruvate kinase, 50 μg/mL lactate dehydrogenase and 200 μM erktide peptide. The reaction is initiated by the addition of 65 μM ATP. The rate of decrease of absorbance at 340 nM is monitored. The IC50 is evaluated from the data as a function of inhibitor concentration.
細胞アッセイ 細胞株 HT29 cells
濃度 ~10 μM
反応時間 48 h
実験の流れ Cell proliferation is measured by 3H-thymidine incorporation. The cells are plated at a concentration of 10,000 cells/well in a 96-well plate using growth media, RPMI 1640 containing 10% FBS. Serially diluted compounds are added. The cells and this compound are incubated for 48 hours at 37°C incubator. After 48 hours, 0.4 μCi of 3H-thymidine is added to each wells for 8 hours and returned to the 37°C incubator. The cells are harvested using a Tomtec 96-well cell harvester and the CPM is determined using the Wallac 1205 BETAPLATE liquid scintillation counter. The IC50 is the 50% inhibition of contr
動物実験 動物モデル NSG mice bearing human melanoma RPDX tumors
投薬量 50 mg/kg BID
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/19827834/
  • https://pubmed.ncbi.nlm.nih.gov/26673799/

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：

Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and calcium [ J Biol Chem, 2025, 301(3):108183] PubMed: 39814226
Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma [ Nat Commun, 2024, 15(1):2581] PubMed: 38519484
Targeting ERK-MYD88 interaction leads to ERK dysregulation and immunogenic cancer cell death [ Nat Commun, 2024, 15(1):7037] PubMed: 39147750
MAPK1 Mediates MAM Disruption and Mitochondrial Dysfunction in Diabetic Kidney Disease via the PACS-2-Dependent Mechanism [ Int J Biol Sci, 2024, 20(2):569-584] PubMed: 38169625
ERK hyperactivation serves as a unified mechanism of escape in intrinsic and acquired CDK4/6 inhibitor resistance in acral lentiginous melanoma [ Oncogene, 2024, 43(6):395-405] PubMed: 38066089
Conformation selection by ATP-competitive inhibitors and allosteric communication in ERK2 [ Elife, 2024, 12RP91507] PubMed: 38537148
Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma [ PLoS One, 2024, 19(1):e0295629] PubMed: 38277404
Enhanced kinase translocation reporters for simultaneous real-time measurement of PKA, ERK, and Ca2 [ bioRxiv, 2024, 2024.09.30.615856] PubMed: 39411162
Differential Effects of Confinement on the Dynamics of Normal and Tumor-Derived Pancreatic Ductal Organoids [ ACS Appl Bio Mater, 2024, 7(12):8489-8502] PubMed: 39576883
Kinase-Modulated Bioluminescent Indicators Enable Noninvasive Imaging of Drug Activity in the Brain [ ACS Cent Sci, 2023, 9(4):719-732] PubMed: 37122464

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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