GCN2iB

Catalog No.S8929

For research use only.

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

GCN2iB Chemical Structure

CAS No. 2183470-12-2

Selleck's GCN2iB has been cited by 1 Publication

Purity & Quality Control

Choose Selective Serine/threonin kinase Inhibitors

Biological Activity

Description GCN2iB is an ATP-competitive serine/threonine-protein kinase general control nonderepressible 2 (GCN2) inhibitor with IC50 of 2.4 nM.
Targets
GCN2 [1]
(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 GCN2iB 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. [1]

In vivo

The combination of ASNase treatment with GCN2iB synergistically blocks in vivo tumor growth in ALL, AML, and pancreatic xenograft models. [1]

Protocol (from reference)

Kinase Assay:

[1]

  • GCN2 kinase assay:

    Recombinant GCN2 (1 nmol/L) protein is pre-incubated with GCN2 inhibitors for 60 min and then incubated with ATP (KM 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.

Cell Research:

[1]

  • Cell lines: Pancreatic cancer cells, CCRF-CEM cells, MEF cells (GCN2-WT or -KO), CCRF-CEM, MV-4-11, SU.86.86 cells
  • Concentrations: 37 nM, 110 nM, 330 nM, 1.0 μM
  • Incubation Time: 4 h, 72 h
  • Method:

    CCRF-CEM cells are treated with GCN2iB as indicated for 4 h. Cell lysates are analyzed by western blot; MEF cells (GCN2-WT or -KO) are treated with GCN2 inhibitors as indicated for 72 h. Cell viability is measured; CCRF-CEM, MV-4-11, and SU.86.86 cells are treated with 1 μmol/L GCN2iB as indicated for 72 h. Cell viability is measured at day 0 and day 3; CCRF-CEM and SU.86.86 cells are treated with GCN2 inhibitors as indicated for 72 h. Cell viability is measured.

Animal Research:

[1]

  • Animal Models: 6-week-old female SCID mice
  • Dosages: 1 mg/kg, 3 mg/kg, 10 mg/kg
  • Administration: Oral gavage, IP

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 451.83
Formula

C18H12ClF2N5O3S

CAS No. 2183470-12-2
Storage 3 years -20°C powder
2 years -80°C in solvent
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

In vivo Formulation Calculator (Clear solution)

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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.

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Molarity Calculator

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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

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