For research use only, not for therapeutic use.
G-749（Cat No.:I001766）is a potent and selective inhibitor of the FLT3 receptor tyrosine kinase, which is commonly mutated in acute myeloid leukemia (AML). By targeting FLT3-ITD mutations, G-749 disrupts key signaling pathways responsible for the proliferation and survival of leukemic cells. Preclinical studies have demonstrated its ability to induce apoptosis and inhibit the growth of AML cells, particularly in cases resistant to other FLT3 inhibitors. G-749 shows promise as a therapeutic candidate for overcoming drug resistance in AML, offering a potential new treatment option for patients with this mutation.
| Catalog Number | I001766 |
| CAS Number | 1457983-28-6 |
| Synonyms | 8-bromo-2-((1-methylpiperidin-4-yl)amino)-4-((4-phenoxyphenyl)amino)pyrido[4,3-d]pyrimidin-5(6H)-one |
| Molecular Formula | C25H25BrN6O2 |
| Purity | ≥95% |
| Target | FLT3 |
| Solubility | DMSO: ≥ 25 mg/mL |
| Storage | Store at -20°C |
| IC50 | 0.4/0.6/3.5/7.5 nM(Wt Flt3/D835Y/MV4-11/Molm-14) |
| IUPAC Name | 8-bromo-2-[(1-methylpiperidin-4-yl)amino]-4-(4-phenoxyanilino)-6H-pyrido[4,3-d]pyrimidin-5-one |
| InChI | InChI=1S/C25H25BrN6O2/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) |
| InChIKey | SXWMIXPJPNCXQQ-UHFFFAOYSA-N |
| SMILES | CN1CCC(CC1)NC2=NC3=C(C(=O)NC=C3Br)C(=N2)NC4=CC=C(C=C4)OC5=CC=CC=C5 |
| Reference | 1:Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia.Lee HK,Kim HW,Lee IY,Lee J,Lee J,Jung DS,Lee SY,Park SH,Hwang H,Choi JS,Kim JH,Kim SW,Kim JK,Cools J,Koh JS,Song HJ, PMID: 24532805 PMCID: PMC3975259 DOI: 10.1182/blood-2013-04-493916 </br><span>Abstract:</span> Aberrant activations of Fms-like tyrosine receptor kinase (FLT) 3 are implicated in the pathogenesis of 20% to 30% of patients with acute myeloid leukemia (AML). G-749 is a novel FLT3 inhibitor that showed 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. G-749 retained its inhibitory potency in various drug-resistance milieus such as patient plasma, FLT3 ligand surge, and stromal protection. Furthermore, it 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 G-749 yielded complete tumor regression and increased life span in animal models. Thus, G-749 appears to be a promising next-generation drug candidate for the treatment of relapsed and refractory AML patients with various FLT3-ITD/FLT3-TKD mutants and further shows the ability to overcome drug resistance. |
