GSK2606414

製品コードS7307 バッチS730702

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

C24H20F3N5O
分子量 451.44 CAS No. 1337531-36-8
Solubility (25°C)* 体外 DMSO 90 mg/mL (199.36 mM)
Ethanol 19 mg/mL (42.08 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 Corn oil
4.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 90 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. 
* <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 GSK2606414 is an orally available, potent, and selective PERK inhibitor with IC50 of 0.4 nM, displaying at least 100-fold selectivity over the other EIF2AKs assayed. GSK2606414 impairs GANT-61 induced autophagy in NB cells with MYCN amplification. GSK2606414 exacerbates ER stress-induced apoptosis in HCT116 cells while reduces the apoptosis in SIL1 KD HeLa cells.
in vitro

GSK2606414 inhibits PERK Autophosphorylation in A459 Cells with IC50 of <0.3 μM. [1]
in vivo

GSK2606414 exhibits high oral availability, and low to moderate blood clearance in mouse, rat, and dog. GSK2606414, administered orally, inhibits tumor growth in a dose-dependent manner in mice bearing pancreatic human BxPC3 tumors. [1]
特徴 The first PERK-selective inhibitor with good oral bioavailability and crosses the blood-brain barrier.

プロトコル(参考用のみ)

キナーゼアッセイ PKR-like Endoplasmic Reticulum Kinase (PERK) Assay (HTRF Format)
GST-PERK cytoplasmic domain is purchased. 6-His-full-length human eIF2α is purified from baculovirus expression in Sf9 insect cells. The eIF2α protein is buffer exchanged by dialysis into PBS, chemically modified by NHS-LC-biotin and then buffer exchanged by dialysis into 50 mM Tris, pH 7.2, 250 mM NaCl, 5 mM DTT. Protein is aliquoted and stored at −80 °C. Quench solution is freshly prepared and when added to the reaction gives final concentrations of 4 nM eIF2α phospho-ser51-antibody, 4 nM Eu-1024 labeled anti-rabbit IgG, 40 nM streptavidin Surelight APC, and 15 mM EDTA. Reactions were performed in black 384-well polystyrene low volume plates in a final volume of 10 μL. The reaction volume contains, in final concentrations, 10 mM HEPES, 5 mM MgCl2, 5 μM ATP, 1 mM DTT, 2 mM CHAPS, 40 nM biotinylated 6-His-eIF2α, and 0.4 nM GST-PERK. Compounds under analysis are dissolved in DMSO to 1.0 mM and serially diluted 1–3 with DMSO through 11 dilutions. An amount of 0.1 μL of each concentration is transferred to the corresponding well of an assay plate. This creates a final compound concentration range from 0.00017 to 10 μM. GST-PERK solution is added to assay plates containing compounds and preincubated for 30 min at room temperature. The reaction is initiated by the addition of ATP and eIF2α substrate solution. After 1 h of incubation, the quench solution is added. The plates are covered for 2 h at room temperature prior to determination of signal. The resulting signal is quantified on a Viewlux reader. The APC signal is normalized to the europium signal by transforming the data through an APC/Eu calculation. The data for concentration response curves are plotted as % inhibition calculated with the data reduction formula 100 × [1 – (U1 – C2)/(C1 – C2)] versus concentration of compound where U is the unknown value, C1 is the average control value obtained for 1% DMSO, and C2 is the average control value obtained for 0.1 M EDTA. Data are fitted with a curve described by where A is the minimum response, B is the maximum response, D is the slope factor, x is the concentration of the compound, and C is the IC50. The results for each compound are recorded as IC50 values.
細胞アッセイ 細胞株 A549 cells
濃度 0.3 μM
反応時間 2 h
実験の流れ

Cells were incubated with PERK inhibitor (GSK2606414, compound 38) and then stimulated with thapsigargin. After 2 h, the cells were lysed and analyzed for inhibition of PERK autophosphorylation.
動物実験 動物モデル BxPC3 human pancreatic xenograft model
投薬量 ~150 mg/kg
投与方法 Oral administration

カスタマーフィードバック

, , Mol Neurobiol, 2016, 54(3):1808-1817

Data from [Data independently produced by , , J Neurosci, 2018, 38(9):2372-2384]

Data from [Data independently produced by , , J Clin Endocrinol Metab, 2017, 102(2):634-643]

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：

Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway [ Exp Mol Med, 2024, 56(2):408-421.] PubMed: 38316963
A RIPK3-independent role of MLKL in suppressing parthanatos promotes immune evasion in hepatocellular carcinoma [ Cell Discov, 2023, 9(1):7] PubMed: 36650126
Nitric oxide-induced ribosome collision activates ribosomal surveillance mechanisms [ Cell Death Dis, 2023, 14(7):467] PubMed: 37495584
Nitric oxide-induced ribosome collision activates ribosomal surveillance mechanisms [ Cell Death Dis, 2023, 14(7):467] PubMed: 37495584
IRE1α arm of unfolded protein response in muscle-specific TGF-β signaling-mediated regulation of muscle cell immunological properties [ Cell Mol Biol Lett, 2023, 28(1):15] PubMed: 36849929
Large HBV Surface Protein-Induced Unfolded Protein Response Dynamically Regulates p27 Degradation in Hepatocellular Carcinoma Progression [ Int J Mol Sci, 2023, 10.3390/ijms241813825] PubMed: 37762128
Acetylshikonin induces apoptosis through the endoplasmic reticulum stress-activated PERK/eIF2α /CHOP axis in oesophageal squamous cell carcinoma [ J Cell Mol Med, 2023, 10.1111/jcmm.18030] PubMed: 37929884
High-Content and High-Throughput Clonogenic Survival Assay Using Fluorescence Barcoding [ Cancers -Basel), 2023, 15(19)4772] PubMed: 37835466
PERK/ATF4-dependent expression of the stress response protein REDD1 promotes proinflammatory cytokine expression in the heart of obese mice [ Am J Physiol Endocrinol Metab, 2023, 324(1):E62-E72] PubMed: 36383638
Nifuroxazide induces the apoptosis of human non‑small cell lung cancer cells through the endoplasmic reticulum stress PERK signaling pathway [ Oncol Lett, 2023, 25(6):248] PubMed: 37153034

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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