GCN2iB

Catalog No.S8929 Batch:S892902

Print

Technical Data

Formula

C18H12ClF2N5O3S
Molecular Weight 451.83 CAS No. 2183470-12-2
Solubility (25°C)* In vitro DMSO 15 mg/mL (33.19 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.75mg/ml 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. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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 Assay:

[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 Study:

[1]
  • Animal Models

    6-week-old female SCID mice

  • Dosages

    1 mg/kg, 3 mg/kg, 10 mg/kg

  • Administration

    Oral gavage, IP

Selleck's GCN2iB has been cited by 2 publications

Nucleus pulposus cells regulate macrophages in degenerated intervertebral discs via the integrated stress response-mediated CCL2/7-CCR2 signaling pathway [ Exp Mol Med, 2024, 56(2):408-421.] PubMed: 38316963
Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence [ Nat Commun, 2021, 12(1):5507] PubMed: 34535653

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.