- ISRIB (trans-isomer)
- GSK2656157
| GSK2606414PERK inhibitor,potent and selective |
Sample solution is provided at 25 µL, 10mM.
Quality Control & MSDS
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- Purity = 98.18%
- COA (Certificate Of Analysis)
- HPLC
- NMR (Nuclear Magnetic Resonance)
- MSDS (Material Safety Data Sheet)
- Datasheet
Chemical structure
Related Biological Data
Related Biological Data
Related Biological Data
| Description | GSK2606414 is a potent and selective inhibitor of protein kinase R-like ER kinase (PERK) with IC50 value of 0.4 nM. | |||||
| Targets | PERK | |||||
| IC50 | 0.4 nM | |||||
| Kinase experiment [1]: | |
PKR-like endoplasmic reticulum kinase (PERK) assay (HTRF Format) | GST-PERK cytoplasmic domain was purchased. 6-His-full-length human eIF2α was purified from baculovirus expression in Sf9 insect cells. The eIF2α protein was 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 was aliquoted and stored at -80°C. Quench solution was 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 were 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 was 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 was added to assay plates containing compounds and preincubated for 30 mins at room temperature. The reaction was initiated by the addition of ATP and eIF2α substrate solution. After 1 hr of incubation, the quench solution was added. The plates were covered for 2 hrs at room temperature prior to determination of signal. The resulting signal was quantified on a Viewlux reader. The APC signal is normalized to the europium signal by transforming the data through an APC/Eu calculation. The results for each compound were recorded as IC50 values. |
| Cell experiment [1]: | |
Cell lines | A459 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
Reaction Conditions | 0.003, 0.1 and 0.3 μM; 2 hrs |
Applications | In A459 cells, GSK2606414 inhibited PERK Autophosphorylation with the IC50 value of < 0.3=""> |
| Animal experiment [1]: | |
Animal models | BxPC3 human pancreatic xenograft model |
Dosage form | ~ 150 mg/kg; p.o. |
Applications | In mice, rats and dogs, GSK2606414 exhibited high oral availability, and low to moderate blood clearance. In mice bearing pancreatic human BxPC3 tumors, GSK2606414 inhibited tumor growth in a dose-dependent manner. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1]. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW, Li WH, Heerding DA, Minthorn E, Mencken T et al: Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-p yrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J Med Chem, 55(16):7193-7207. | |
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| Cas No. | 1337531-36-8 | SDF | Download SDF |
| Synonyms | GSK 2606414;GSK-2606414 | ||
| Chemical Name | 1-[5-(4-amino-7-methylpyrrolo[2,3-d]pyrimidin-5-yl)-2,3-dihydroindol-1-yl]-2-[3-(trifluoromethyl)phenyl]ethanone | ||
| Canonical SMILES | CN1C=C(C2=C1N=CN=C2N)C3=CC4=C(C=C3)N(CC4)C(=O)CC5=CC(=CC=C5)C(F)(F)F | ||
| Formula | C24H20F3N5O | M.Wt | 451.44 |
| Solubility | ≥22.57 mg/mL in DMSO, ≥12.03 mg/mL in EtOH with ultrasonic and warming, <2.19 mg/ml="" in="" h2o=""> | Storage | Store at -20°C |
| Physical Appearance | A solid | Shipping Condition | Evaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon request |
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. | ||
GSK2606414 is a selective inhibitor of PERK with IC50 value of 0.4nM.[1]PERK (PRKR-like endoplasmic reticulum kinase or protein kinase R (PKR)-like endoplasmic reticulum kinase) is also known as EIF2AK3 (Eukaryotic translation initiation factor 2-alpha kinase 3). PERK is encoded by EIF2AK3 gene. It belongs to type I membrane protein family. It located in the ER (endoplasmic reticulum) and is induced by ER stress which is caused from malfolded proteins. It causes the inactive of EIF2 (eukaryotic translation-initiation factor 2) by phosphorylating the alpha subunit. PERK can lead to repression of global protein synthesis and a rapid reduction of translational initiation. PERK has been identified to interact with NFE2L2 and DNAJC3. PERK mutation is related to WRS (Wolcott-Rallison syndrome) which is a autosomal recessive disorder with multiple epiphyseal dysplasia,infancy-onset diabetes mellitus, osteopenia, mental retardation, and hepatic and renal dysfunction. [2]GSK2606414 inhibits the activity of PERK with IC50 of 0.4 nM by measuring the cytoplasmic PERK domain phosphorylation. GSK2606414 directly bind to PERK as measured in X-ray structure. GSK2606414 completely inhibit PERK phosphorylation at 30 nM in A549 cells. GSK2606414 has selective inhibition effect on PERK compared to a panel of 294 kinases. There only 20 protein kinases except PERK inhibited >85% by GSK2606414 at 10 μM. GSK2606414 inhibited tumor growth with a dose-dependent manner from 50 to 150 mg/kg in mice bearing pancreatic human BxPC3 tumors.[1]References: [1]. Axten JM, Medina JR, Feng Y, Shu A, Romeril SP, Grant SW, Li WH, Heerding DA, Minthorn E, Mencken T et al: Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-p yrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK). J Med Chem, 55(16):7193-7207.[2]. Shi Y, An J, Liang J, Hayes SE, Sandusky GE, Stramm LE, Yang NN: Characterization of a mutant pancreatic eIF-2alpha kinase, PEK, and co-localization with somatostatin in islet delta cells. J Biol Chem 1999, 274(9):5723-5730.
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请教大家一个问题，不同厂家cIEF的Marker能混合使用吗？另外，如果我对其它厂家pI值为6.0的marker进行cIEF测定，那测得的pI值会等于6.0吗？谢谢！
连续三次都这样，Marker的泳道的位置有很多亮条带，但Marker本来的条带是不亮的。我做了内参和目的，一张胶上左右两部分分别都加样品和Marker，切开转膜分别孵育，一块儿显影，内参的Marker就不会亮，只有目的那一张Marker会亮，昨天做的借了别人的Marker，显影出来还是有那个条带。
我的目的条带还没有Marker那部分的条带亮，Marker的部分非常亮。
英 [?mɑ:k?(r)] 美 [?mɑ:rk?(r)]n.标识，标记； 记号笔，阅卷人； 防守队员； 特征复数： markers
双语例句
Draw your child's outline with a heavy black marker.用浓黑色的毡笔画出你孩子的轮廓。2. He put a marker in his book and followed her out.
他在书里夹了一个书签后便随她出去了。
3. He placed a marker where the ball had landed.他在球落地的地方放了个标记。
4. Step off twenty feet and then place a marker in the ground.先步测20英尺,再在地上做出标记.
5. Step out ten feet and then put a marker in the ground.步测十英尺,然后在地上做出标记.
湿转,跑胶结束后能看到Marker,转膜条件：300mA,150min,因为目的蛋白160kd左右所以时间比较久.转完之后pvdf膜上却未看到marker,丽春红染色可隐约看到一个条带,请问有哪位高人晓得原因么
想看下人肿瘤组织内巨噬细胞的浸润情况，我以为一个CD11b就够了。咨询了一下抗体公司，竟然让我订三个抗体，分别是CD11b，CD68和CD163，后两者不是M1和M2的分型吗？
另外查了下CD11b也确实在别的一些免疫细胞有所表达，请教下，有专门的特异性抗体吗？没课题没经费，只能省省省了
