| Identification | Back Directory | [Name]
G-749 | [CAS]
1457983-28-6 | [Synonyms]
G-49
G-749
G-749, >=98%
G-749 (Free base)
8-Bromo-2-[(1-methyl-4-piperidinyl)amino]-4-[(4-phenoxyphenyl)amino]pyrido[4,3-d]pyrimidin-5(6H)-one
8-Bromo-2-[(1-methyl-4-piperidinyl)amino]-4-[(4-phenoxyphenyl)amino]pyrido[4,3-d]pyrimidin-5(6H)-one G749 | [Molecular Formula]
C25H25BrN6O2 | [MDL Number]
MFCD28167815 | [MOL File]
1457983-28-6.mol | [Molecular Weight]
521.409 |
| Chemical Properties | Back Directory | [density ]
1.487±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
≥26.05 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O | [form ]
solid | [pka]
8.32±0.40(Predicted) |
| Questions And Answer | Back Directory | [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. | [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. | [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. |
| Hazard Information | Back Directory | [Uses]
G-749 is a potent FLT3 inhibitor. It shows lower potency against other tyrosine kinases. | [References]
1. lee h k, kim h w, lee i y, et al. g-749, a novel flt3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. blood, 2014, 123(14): 2209-2219. |
|
|