G-749

• CAT Number: I001766
• CAS Number: 1457983-28-6
• Molecular Formula: C25H25BrN6O2
• Molecular Weight: 521.4
• 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) [1]
• 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: BrC1=CNC(C2=C1N=C(NC3CCN(C)CC3)N=C2NC4=CC=C(OC5=CC=CC=C5)C=C4)=O

G-749 (Cat.No:I001766) is a promising compound with potent activity as a FLT3 inhibitor. It effectively targets FLT3 (WT), FLT3 (D835Y), and Mer with IC50 values of 0.4nM, 0.6nM, and 1nM, respectively. In preclinical studies, G-749 demonstrated inhibition of FLT3 phosphorylation, induction of apoptosis, and anti-proliferative effects in leukemia cells, including those with FLT3-ITD mutations. 

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 Abstract: 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.