Home Metabolism Serine/threonin kinase inhibitor GCN2iB For research use only.

GCN2iB

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

GCN2iB Chemical Structure

GCN2iB Chemical Structure

CAS No. 2183470-12-2

Purity & Quality Control

GCN2iB Related Products

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
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]
Kinase Assay 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 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.
In Vivo
In vivo

The combination of ASNase treatment with GCN2iB synergistically blocks in vivo tumor growth in ALL, AML, and pancreatic xenograft models. [1]
Animal Research Animal Models 6-week-old female SCID mice
Dosages 1 mg/kg, 3 mg/kg, 10 mg/kg
Administration Oral gavage, IP

Chemical Information & Solubility

Molecular Weight 451.83 Formula

C18H12ClF2N5O3S
CAS No. 2183470-12-2 SDF --
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
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 15 mg/mL ( (33.19 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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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