Antibodies
GSK2656157
- 貨號 Cat. No.
- S7033
- 規格 Size
- 50mgã€100mg
- 品牌 Brand
- Selleckchem
Description
GSK2656157
Catalog No.S7033
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.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | 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. | |||||
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| Targets | PERK | |||||
| IC50 | 0.9 nM [1] | |||||
| In vitro | 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 | 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] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [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. |
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Cell Assay: [1]
| Cell lines | human tumor cell lines, primary human microvascular endothelial cells |
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| Concentrations | ~3 μM |
| Incubation Time | 3 day |
| Method | 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. |
Animal Study: [1]
| Animal Models | human tumor xenograft models |
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| Dosages | 50 or 150 mg/kg, twice daily |
| Administration | Orally |
References
Chemical Information
| Molecular Weight (MW) | 416.45 |
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| Formula | C23H21FN6O |
| CAS No. | 1337532-29-2 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 37 mg/mL (88 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 2 mg/mL (4 mM) | ||
| * <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. | |||
| Chemical Name | 1-(5-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-4-fluoroindolin-1-yl)-2-(6-methylpyridin-2-yl)ethanone |
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