Home Angiogenesis FLT3 inhibitor G-749 For research use only.

G-749

G-749 is a novel and potent FLT3 inhibitor with IC50 of 0.4 nM, 0.6 nM and 1 nM for FLT3 (WT), FLT3 (D835Y), and Mer, respectively, showing lower potency against other tyrosine kinases.

G-749 Chemical Structure

G-749 Chemical Structure

CAS No. 1457983-28-6

Purity & Quality Control

G-749 Related Products

Signaling Pathway

FLT3 Signaling Pathways

FLT3 Signaling Pathway

Biological Activity

Description G-749 is a novel and potent FLT3 inhibitor with IC50 of 0.4 nM, 0.6 nM and 1 nM for FLT3 (WT), FLT3 (D835Y), and Mer, respectively, showing lower potency against other tyrosine kinases.
Targets
FLT3 [1]
(Cell-free assay)		 FLT3 (D835Y) [1]
(Cell-free assay)		 Mer [1]
(Cell-free assay)		 Aurora B [1]
(Cell-free assay)		 RET [1]
(Cell-free assay)		 Click to View More Targets
0.4 nM 0.6 nM 1 nM 6 nM 9 nM
In vitro
In vitro In FLT3-WT-bearing RS4-11 cells and FLT3-ITD-harboring MV4-11 and Molm-14 cells, G-749 potently inhibits autophosphorylation of FLT3 with IC50 of ≤8 nM. In leukemia cells, G-749 shows antiproliferative activity by inducing apoptosis. In BaF3 cell lines that stably express FLT3-ITD/N676D, FLT3-ITD/F691L, FLT3-D835Y, or FLT3-D835Y/N676D, G-749 shows strong inhibitory activity with IC50 of <10 nM, and thus overcomes drug resistance. In blasts of AML patients, G-749 also exhibits potent antileukemia activity. [1]
Kinase Assay Kinase assay
Activity assays are conducted using Lance Ultra time-resolved fluorescence resonance energy transfer (TR-FRET) technology from Perkin-Elmer. Briefly, 10 ng/mL FLT3 enzyme, a serial diluted G-749, 80 nM substrate of ULight-poly-GT peptide and variable amounts of ATP (8.5 µM to 1088 μM) are mixed in kinase assay buffer (50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT and 0.01% Tween-20) and are added to a 384-well OptiPlate-384 in a volume of 10 μL. Kinase reactions are incubated at room temperature for up to 1 h and then stopped by the addition of 5 μL of 10 mM EDTA. A volume of 5 μL of the specific Eu-labeled-anti-phosphopeptide antibody diluted in LANCE Detection Buffer is then added to a final concentration of 2 nM. After 30-minute incubation, assay plates are incubated at 23°C and the LANCE signal is measured on an EnVision Multilabel Reader. Excitation wavelength is set at 320 nm and emission monitored at 615 nm (donor) and 665 nm (acceptor). The IC50 is calculated using nonlinear regression analysis analysis by GradPad Prism 5.
Cell Research Cell lines MV4-11, RS4-11, K562, HEL, and Molm-14 cells
Concentrations ~1 μM
Incubation Time 72 hours
Method

Cells are seeded at a density of 2 ×104 cells per well and treated with the indicated concentrations of test inhibitor for 72 hours at 37℃. The conditioned medium (CM) is prepared from HS-5 cell culture for 5 days under routine culture conditions, clarified by centrifugation, and used immediately. The CM is added to complete medium at a final concentration of 35%. In coculture experiments, 5 ×104 AML blast cells are plated in 24-well plates containing 1 ×104 HS-5 monolayers and then cultured for at least 48 hours before the exposure of inhibitors. Cell viability is determined by an ATPLite assay.
In Vivo
In vivo In MV4-11 xenograft mice, G-749 (30 mg/kg p.o.) effectively inhibits the FLT3 pathway and significant inhibits tumor growth. In an orthogonal model of bone marrow engraftment using Molm-14 cells, G-749 (20 mg/kg p.o.) also inhibits tumor growth and increases survival. [1]
Animal Research Animal Models MV4-11 xenograft mouse model and Molm-14 orthogonal mouse model
Dosages ~30 mg/kg
Administration p.o.

Chemical Information & Solubility

Molecular Weight 521.41 Formula

C25H25BrN6O2
CAS No. 1457983-28-6 SDF Download G-749 SDF
Smiles CN1CCC(CC1)NC2=NC3=C(C(=O)NC=C3Br)C(=N2)NC4=CC=C(C=C4)OC5=CC=CC=C5
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 24 mg/mL ( (46.02 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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