Avapritinib 是选择性的、高效的、具有口服活性的KIT和PDGFRA激活环突变激酶抑制剂,能够作用于 KIT D816V (IC50:0.27 nM) 和 PDGFRA D842V (IC50:0.24 nM)。它减弱 ABCB1 和 ABCG2 的传输功能。它与激酶的活性构象结合,并显示抗肿瘤活性。
产品描述
Avapritinib is a dual inhibitor of the mutant KIT receptor (KIT D816V, IC50: 0.27 nM) and PDGFRα (PDGFRα D842V, IC50: 0.24 nM).
体外活性
Cellular activity of Avapritinib on KIT D816 mutants is measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC50=4 and 22 nM, respectively. In Kasumi-1 cells, at positive AML cell line with a KIT exon 17 N822K mutation, Avapritinib potently inhibits KIT N822K mutant autophosphorylation (IC50: 40 nM), downstream signaling, as well as cellular proliferation (IC50: 75 nM)[1].
体内活性
BLU-285 (0.3-30 mg/kg) reduces tumor volume in a P815 KITD814Y mastocytoma allograft mouse model and a GIST patient-derived mouse xenograft model in a dose-dependent manner. Formulations containing BLU-285 have been used to treat KIT- and PDGFRα-driven malignancies.
动物实验
A Kasumi-1 luc+ AML NOG SCID mouse femoral injection model is used to assess the efficacy of Avapritinib (BLU-285) in KIT exon 17-mutated CBF-AML. Following a 21 day post-injection latency period, mice are dosed with Avapritinib orally, once daily at 10 mg/kg or 30 mg/kg through day 45. Control groups are treated with vehicle or Cytarabine administered 100 mg/kg i.p once weekly.
Cas No.
1703793-34-3
分子式
C26H27FN10
分子量
498.57
别名
BLU-285
储存和溶解度
H2O:Insoluble
Ethanol:3 mg/mL
DMSO:65 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years