| Stereochemistry | ACHIRAL |
| Molecular Formula | C25H25BrN6O2.ClH |
| Molecular Weight | 557.87 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN1CCC(CC1)NC2=NC(NC3=CC=C(OC4=CC=CC=C4)C=C3)=C5C(=O)NC=C(Br)C5=N2
InChI
InChIKey=UDYYCTJUUMIMHX-UHFFFAOYSA-N
InChI=1S/C25H25BrN6O2.ClH/c1-32-13-11-17(12-14-32)29-25-30-22-20(26)15-27-24(33)21(22)23(31-25)28-16-7-9-19(10-8-16)34-18-5-3-2-4-6-18;/h2-10,15,17H,11-14H2,1H3,(H,27,33)(H2,28,29,30,31);1H
| Molecular Formula | C25H25BrN6O2 |
| Molecular Weight | 521.409 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
G749 is a Fms-like tyrosine receptor kinase 3 (FLT3) inhibitor and a promising next-generation drug candidate for the treatment of relapsed and refractory acute myeloid leukemia (AML) patients with various FLT3-ITD/FLT3-TKD mutants that shows the ability to overcome drug resistance. It demonstrated potent and sustained inhibition of the FLT3 wild type and mutants including FLT3-ITD, FLT3-D835Y, FLT3-ITD/N676D, and FLT3-ITD/F691L in cellular assays. G749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. It also displayed potent antileukemic activity in bone marrow blasts from AML patients regardless of FLT3 mutation status, including those with little or only minor responses to AC220 or PKC412. Oral administration of G749 yielded complete tumor regression and increased life span in animal models.
Originator
Approval Year
PubMed
Patents
Sample Use Guides
To examine its antitumor efficacy, G749 HCl salt was administered orally every day for 28 days to the MV4-11 xenograft mice.
Route of Administration:
Oral
The antiproliferative activity of G749 was assessed in several leukemia cell lines. Five human leukemia cell lines seeded at a density of 2 × 10(4) cells per well were incubated with increasing concentrations of G749 (0.32, 1.6, 8, 40, 200, 1000, 5000 nM) for 72 hours at 37°C. G749 showed strong antiproliferation of leukemia cells addicted to FLT3-ITD (MV4-11 and Molm-14) in a dose-dependent manner, whereas it did not potently inhibit proliferation of leukemia cells without FLT3 expression (HEL and K562) or of non–FLT3-addicted cells with FLT3-WT (RS4-11).
