GSK2656157 化学構造
分子量: 416.45

高品質保証

カスタマーフィードバック(1)

Quality Control & MSDS

製品説明

  • Compare PERK Inhibitors
    PERK製品生物活性の比較

製品の説明

生物活性

製品説明 GSK2656157 is an ATP-competitive and highly selective inhibitor of PERK with IC50 of 0.9 nM, 500-fold greater against a panel of 300 kinases.
ターゲット

PERK

IC50

0.9 nM [1]

In vitro試験 Pretreatment of cells with GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2a, ATF4, and CHOP with an IC50 in the range of 10-30 nM. Cells that are exposed to 1 mM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis. Five of 84 UPR-related genes (DDIT3, HERPUD1, PPP1R15A, C/EBP-beta, and ERN1) are down regulated more than 4-fold by GSK2656157. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM. Thus, GSK2656157 can be used to evaluate the biologic function of PERK in various biologic contexts. [1]
In vivo試験 Complete inhibition of phospho-PERK Thr980 is observed through 8 hours after a single 50 mg/kg oral dose of GSK2656157. Treatment of mice with 50 or 150 mg/kg twice daily dosing of GSK2656157 results in dose-dependent inhibition of tumor growth in four models; reaching 54–114% tumor growth inhibition at the 150 mg/kg, twice daily dose. Altered amino acid metabolism, decreased blood vessel density, and vascular perfusion are potential mechanisms for the observed antitumor effect. Treatment of mice with GSK2656157 results in inhibition of tumor growth in multiple human tumor xenografts. [1]
臨床試験
特集 Orally bioavailable PERK-selective inhibitor that functions independent of eIF2α phosphorylation.

プロトコル (参考用のみ)

キナーゼアッセイ:

[1]

Kinase assay Inhibitory potency of GSK2656157 is measured using recombinant GST-PERK (536–1116 amino acids) with 6-His-full-length human eIF2a as a substrate. Kinase selectivity is evaluated using 27 kinases at GSK as well as a panel of 300 kinases.

細胞アッセイ:

[1]

細胞株 human tumor cell lines, primary human microvascular endothelial cells
濃度 ~3 μM
反応時間 3 day
実験の流れ

Antiproliferative activity of GSK2656157 against multiple human tumor cell lines as well as primary human microvascular endothelial cells is evaluated in a 3-day proliferation assay using standard culture medium. In the absence of exogeneous UPR inducers, GSK2656157 has no significant effect on the growth of any of these cells with IC50 range of 6–25 mM.

動物実験:

[1]

動物モデル human tumor xenograft models
製剤 0.5% hydroxypropyl methyl cellulose, 0.1% tween-80 in water (pH 6.75).
投薬量 50 or 150 mg/kg, twice daily
投与方法 Orally

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download GSK2656157 SDF
分子量 416.45
化学式

C23H21FN6O

CAS No. 1337532-29-2
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 32 mg/mL (76.83 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo
* <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.
化学名 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone

カスタマーフィードバック (1)


Click to enlarge
Rating
Source , , Cell Res, 2015, 25: 946-962. GSK2656157 purchased from Selleck
Method Immunoblotting Analysis
Cell Lines kri1lcas002 HSPCs
Concentrations 20 µM
Incubation Time 3 h
Results Live imaging and immunoblotting analysis further revealed that GSK2656157 treatment inhibited the formation of autophagosomes indicated by LC3-II Puncta.

文献中の引用 (2)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related PERK 阻害剤

最近チェックしたアイテム

Tags: GSK2656157を買う | GSK2656157供給者 | GSK2656157を購入する | GSK2656157費用 | GSK2656157生産者 | オーダーGSK2656157 | GSK2656157代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
お問い合わせ