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Denfivontinib

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Chemical Structure| 1457983-28-6 同义名 : G-749
CAS号 : 1457983-28-6
货号 : A845930
分子式 : C25H25BrN6O2
纯度 : 99%+
分子量 : 521.409
MDL号 : MFCD28167815
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(47.95 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • FLT3

    FLT3 (D835Y), IC50:0.4 nM

    FLT3, IC50:0.4 nM
描述 Acute myeloid leukemia (AML) is an aggressive hematologic disorder in which the hematopoietic progenitor cells lose their ability to differentiate normally and continue to proliferate. Fms-like tyrosine receptor kinase (FLT) 3 plays an important role in normal hematopoiesis and leukemogenesis and is expressed in most AML blasts. G-749 is a novel and effective FLT3 inhibitor with IC50s of 0.4 nM, 0.6 nM and 1 nM for FLT3 (WT), FLT3 (D835Y) and Mer, respectively. G-749 inhibited autophosphorylation of FLT3 with an IC50 value of ≤8 nM in FLT3-WT bearing RS4-11 and in FLT3-ITD harboring MV4-11 and Molm-14 cells. The antiproliferative activity of G-749 was assessed in several leukemia cell lines where it showed strong antiproliferation of leukemia cells addicted to FLT3-ITD (MV4-11 and Molm-14) in a dose-dependent manner. The BaF3 cells expressing the indicated FLT3 mutations were incubated for 2 h with G-749, and G-749 showed strong potency against autophosphorylation of all tested FLT3 mutants with IC50 of <10 nM. A single dose of G-749 HCl salt (10 mg/kg) was administered orally to subcutaneous MV4-11 xenograft mice and showed sustained inhibition of p-FLT3, p-STAT5, and p-ERK1/2, which indicated that G-749 effectively inhibits the FLT3 pathway and that its inhibition lasts for 24 h. Antitumor efficacy was examined with the MV4-11 xenograft mice using G-749 HCl salt (administered orally every day for 28 days). Significant inhibition of tumor growth was observed in the 3 mg/kg per day dosing group from 4 days onward, and apparent tumor regression was seen in the 10 and 30 mg/kg per day dosing group[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.92mL

0.38mL

0.19mL

9.59mL

1.92mL

0.96mL

19.18mL

3.84mL

1.92mL
参考文献

[1]Lee HK, Kim HW, et al. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19.

[2]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. G-749, a novel FLT3 kinase inhibitor, can overcome drug resistance for the treatment of acute myeloid leukemia. Blood. 2014 Apr 3;123(14):2209-19. doi: 10.1182/blood-2013-04-493916. Epub 2014 Feb 14. PMID: 24532805; PMCID: PMC3975259.