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GCN2iB GCN2 Inhibitor

Name: GCN2iB
Brand: Selleck Chemicals
SKU: S8929
Availability: InStock
Rating: 5 (6 reviews)

Cat.No.S8929

GCN2iB is an ATP-competitive serine/threonine-protein kinase general control nonderepressible 2 (GCN2) inhibitor with IC50 of 2.4 nM.

Chemical Structure

Molecular Weight: 451.83

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Quality Control

Batch: Purity: 99.03%

99.03

Related Targets	Dehydrogenase HSP Transferase P450 (e.g. CYP17) PDE phosphatase PPAR Vitamin Carbohydrate Metabolism Mitochondrial Metabolism
Other Serine/threonin kinase Inhibitors	WNK463 SRPIN340 Benzamidine HCl SPHINX31 BAY-1816032 ML281 DCLK1-IN-1 SGC-GAK-1 WNK-IN-11 MKI-1

Solubility

In vitro
Batch:

DMSO : 15 mg/mL (33.19 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.750mg/ml (1.66mM)	Taking the 1 mL working solution as an example, add 50 μL of 15 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.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

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.

Chemical Information, Storage & Stability

Molecular Weight	451.83	Formula	C₁₈H₁₂ClF₂N₅O₃S	Storage (From the date of receipt)	3 years -20°C powder
CAS No.	2183470-12-2	--		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	COC1=C(C=C(C=N1)Cl)S(=O)(=O)NC2=C(C(=C(C=C2)F)C#CC3=CN=C(N=C3)N)F

Mechanism of Action

Targets/IC₅₀/Ki	GCN2 (Cell-free assay) 2.4 nM
In vitro	The treatment of acute lymphoblastic leukemia (ALL) cells with GCN2iB renders ALL cells sensitive to ASNase by preventing the induction of ASNS, resulting in reduced levels of de novo protein synthesis. Combined treatment with ASNase and this compound induces the stress-activated MAPK pathway, thereby triggering apoptosis. By using cell-panel analyses, we also shows that acute myelogenous leukemia and pancreatic cancer cells are highly sensitive to the combined treatment.
Kinase Assay	GCN2 kinase assay
Kinase Assay	Recombinant GCN2 (1 nmol/L) protein is pre-incubated with GCN2iB for 60 min and then incubated with ATP (K_M value of GCN2 = 190 μmol/L) and the green fluorescent protein-eIF2α substrate (130 nmol/L) at 25°C. The amount of phosphorylated substrate is determined using the LanthaScreen Tb-anti-p-eIF2α (pSer52) antibody kit. The IC50 value of eIF2α kinase is measured using the XLfit software.
In vivo	The combination of ASNase treatment with GCN2iB synergistically blocks in vivo tumor growth in ALL, AML, and pancreatic xenograft models.
References	[1] https://pubmed.ncbi.nlm.nih.gov/30061420/

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