Choose Your Country or Region

GSK2606414

Name: GSK2606414
Brand: Selleck Chemicals
SKU: S7307
Rating: 5 (90 reviews)

Catalog No.S7307 Purity:99.92%

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.

GSK2606414 Chemical Structure

CAS No. 1337531-36-8

Purity & Quality Control

Batch: Purity: 99.92%

99.92

GSK2606414 Related Products

Related Products	GSK2656157 Salubrinal ISRIB (trans-isomer) Sal003 Azoramide BTdCPU CCT020312	Click to Expand
Related Compound Libraries	Autophagy Compound Library Apoptosis Compound Library Ferroptosis Compound Library Pyroptosis Compound Library Mitochondria-Targeted Compound Library	Click to Expand

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
L929	Anti-neprotic assay			Anti-neprotic activity in mouse L929 cells assessed as reduction in TNF-induced necroptosis and measured every 1 hr by SYTOX Green dye based fluorescence assay, IC50=0.0004μM.	31622096
MEF	Anti-neprotic assay			Anti-neprotic activity in mouse MEF cells assessed as reduction in TNF-induced necroptosis and measured every 1 hr in presence of z-VAD by SYTOX Green dye based fluorescence assay, IC50=0.0073μM.	31622096
A549	Function assay		2 hrs	Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells after 2 hrs by Western blotting, IC50<0.03μM.	22827572
A549	Function assay		1 hr	Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells preincubated for 1 hr followed by thapsigargin-induction measured after 1 hr by Western blotting analysis, IC50<0.03μM.	24900593
A549	Function assay	0.03 uM	2 hrs	Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells at 0.03 uM after 2 hrs by Western blotting	22827572
Caco-2	Function assay		48 hours	Determination of IC50 values for inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells after 48 hours by high content imaging, IC50=0.25μM.	ChEMBL
Click to View More Cell Line Experimental Data

Biological Activity

Description

Features

The first PERK-selective inhibitor with good oral bioavailability and crosses the blood-brain barrier.

Targets

EIF2AK3 (PERK) ^[1]
(Cell-free assay)

0.4 nM

In vitro
In vitro	GSK2606414 inhibits PERK Autophosphorylation in A459 Cells with IC50 of <0.3 μM. ^[1]
Kinase Assay	PKR-like Endoplasmic Reticulum Kinase (PERK) Assay (HTRF Format)
Kinase Assay	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.
Cell Research	Cell lines	A549 cells
	Concentrations	0.3 μM
	Incubation Time	2 h
	Method	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.
Experimental Result Images	Methods	Biomarkers	Images	PMID
Experimental Result Images	Western blot	p-PERK / PERK p-KIT / KIT / p-STAT5 / p-ERK		28332979

In Vivo
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]
Animal Research	Animal Models	BxPC3 human pancreatic xenograft model
	Dosages	~150 mg/kg
	Administration	Oral administration

References

[1] Axten JM, et al. J Med Chem. 2012, 55(16), 7193-7207.

Chemical Information & Solubility

Molecular Weight	451.44	Formula	C₂₄H₂₀F₃N₅O
CAS No.	1337531-36-8	SDF	Download GSK2606414 SDF
Smiles	CN1C=C(C2=C(N=CN=C21)N)C3=CC4=C(C=C3)N(CC4)C(=O)CC5=CC(=CC=C5)C(F)(F)F
Storage (From the date of receipt)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

In vitro
Batch:

DMSO : 90 mg/mL ( (199.36 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 19 mg/mL

Water : Insoluble

Molecular Weight Calculator

In vivo Batch: Add solvents to the product individually and in order.					In vivo Formulation Calculator
	Clear solution	5%DMSO 1 Corn oil	4.5mg/ml (9.97mM)	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.	In vivo Formulation Calculator
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	10.0mg/ml (22.15mM)	Taking the 1 mL working solution as an example, add 50 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil	0.9mg/ml (1.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 18 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.
Clear solution	5% DMSO 1 45% PEG 300 2 ddH2O	1.0mg/ml (2.22mM)	Taking the 1 mL working solution as an example, add 50 μL of 20 mg/ml clarified DMSO stock solution to 450 μL PEG 300, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):