[CAS NO. 1337532-29-2] GSK2656157
PRODUCTS SPECIFICATIONS [1337532-29-2]
DESCRIPTION [1337532-29-2]
Overview
| MDL | MFCD27997885 |
|---|---|
| Molecular Weight | 416.45 |
| Molecular Formula | C23H21FN6O |
| SMILES | CC1=CC=CC(CC(N2CCC3=C2C=CC(C4=CN(C)C5=NC=NC(N)=C54)=C3F)=O)=N1 |
26 Publications Citing Use of MCE
- [1]Cell Metab. 2022 Mar 8;S1550-4131(22)00054-7.
- [2]Sci Adv. 2021 Jun 16;7(25):eabf8577.
- [3]Nat Commun. 2022 Oct 16;13(1):6108.
- [4]Cell Death Dis. 2021 Nov 1;12(11):1038.
- [5]Cell Biol Toxicol. 2022 Jan 14.
- [6]Cell Discov. 2021 Oct 26;7(1):98.
- [7]Free Radic Biol Med. 2021 Sep 11;S0891-5849(21)00721-8.
- [8]NPJ Breast Cancer. 2022 Jan 10;8(1):2.
- [9]J Pathol. 2020 Jun;251(2):123-134.
- [10]J Neuroinflammation. 2017 May 11;14(1):104.
- [11]Oxid Med Cell Longev. 05 Aug 2022.
- [12]Oxid Med Cell Longev. 2020 Jul 27;2020:8291413.
- [13]FASEB J. 2022 Jul;36(7):e22401.
- [14]Ecotoxicol Environ Saf. 2022 Jun 15;238:113595.
- [15]Int J Mol Sci. 2017 Apr 18;18(4). pii: E854.
- [16]Cancer Cell Int. 2017 Jan 10;17:12.
- [17]Vascul Pharmacol. 2018 Oct;109:36-44.
- [18]J Steroid Biochem Mol Biol. 2021, 105893.
- [19]J Funct Foods. July 2022, 105116.
- [20]Appl Microbiol Biotechnol. 2020 Nov 20;1-14.
- [21]Brain Res Bull. 2020 Sep;162:73-83.
- [22]Brain Res Bull. 2019 Mar;146:28-39.
- [23]Biomarkers. 2022 Apr 21;1-13.
- [24]Animals (Basel). 2021 Nov 28;11(12):3400.
- [25]Fish and Shellfish Immunology Reports. 2020, 100002.
- [26]Methods Mol Biol. 2018;1711:351-398.
Summary
GSK2656157 is a selective and ATP-competitive inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase ( PERK ) with an IC 50 of 0.9 nM.
IC50 & Target
|
EIF2AK3 (PERK) 0.9 nM (IC 50 ) |
EIF2AK1 (HRI) 460 nM (IC 50 ) |
BRK 905 nM (IC 50 ) |
EIF2AK2 (PKR) 905 nM (IC 50 ) |
MEKK3 954 nM (IC 50 ) |
Aurora B 1259 nM (IC 50 ) |
||
|
KHS 1764 nM (IC 50 ) |
LCK 2344 nM (IC 50 ) |
MLK2 2796 nM (IC 50 ) |
MEKK3 2847 nM (IC 50 ) |
ALK5 3020 nM (IC 50 ) |
MLCK2 3039 nM (IC 50 ) |
||
|
EIF2AK4(GCN2) 3162 nM (IC 50 ) |
c-MER 3431 nM (IC 50 ) |
PI3Kγ 3802 nM (IC 50 ) |
WNK3 5951 nM (IC 50 ) |
LRRK2 6918 nM (IC 50 ) |
ROCK1 7244 nM (IC 50 ) |
||
|
MSK1 8985 nM (IC 50 ) |
NEK1 9807 nM (IC 50 ) |
AXL 9808 nM (IC 50 ) |
JAK2 24547 nM (IC 50 ) |
||||
In Vitro
GSK2656157 results in inhibition of PERK activation as well as decreases in the downstream substrates, phospho-eIF2α, ATF4, and CHOP with an IC 50 in the range of 10-30 nM in the BxPC3 pancreatic tumor cell line. Cells that are exposed to 1 μM GSK2656157 before UPR induction are able to block this effect on de novo protein synthesis [1] . GSK2656157 causes the activation of another eIF2α kinase to compensate for the loss of PERK activity in HT1080 cells. GSK2656157 inhibits the growth of the HT1080 cells [2] . GSK2656157 inhibits LPS-induced IL-1β production, LPS-induced Caspase 1 activation and LPS-induced eIF-2α phosphorylation, but does not inhibit LPS-induced TNF-α production [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
GSK2656157 (1.5-150 mg/kg, p.o.) results in dose-dependent inhibition of phospho-PERK Thr980, with more than 80% inhibition at 50 and 150 mg/kg. GSK2656157 (50-150 mg/kg, p.o.) results in dose-dependent inhibition of tumor growth in human tumor xenograft models [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
1M HCl : 100 mg/mL ( 240.12 mM ; ultrasonic and adjust pH to 1 with HCl)
DMSO : 8.33 mg/mL ( 20.00 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4012 mL | 12.0062 mL | 24.0125 mL |
| 5 mM | 0.4802 mL | 2.4012 mL | 4.8025 mL |
| 10 mM | 0.2401 mL | 1.2006 mL | 2.4012 mL |
-
1.
Add each solvent one by one: 0.5% HPMC >> 0.2%Tween80
Solubility: 4.17 mg/mL (10.01 mM); Suspended solution; Need ultrasonic
-
2.
-
3.
Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)
Solubility: ≥ 0.5 mg/mL (1.20 mM); Clear solution
-
4.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 0.5 mg/mL (1.20 mM); Clear solution
References
- [1] Atkins C, et al. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res. 2013 Mar 15;73(6):1993-2002.
- [2] Krishnamoorthy J, et al. Evidence for eIF2α phosphorylation-independent effects of GSK2656157, a novel catalytic inhibitor of PERK with clinical implications. Cell Cycle. 2014 Mar 1;13(5):801-6.
- [3] Ando T, et al. GSK2656157, a PERK inhibitor, reduced LPS-induced IL-1β production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells. Immunopharmacol Immunotoxicol. 2016 Aug;38(4):298-302.
- [4] Zhao Q, et al. Thioredoxin-interacting protein links endoplasmic reticulum stress to inflammatory brain injury and apoptosis after subarachnoid haemorrhage. J Neuroinflammation. 2017 May 11;14(1):104.
Synonyms