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。

Avapritinib is a dual inhibitor of the mutant KIT receptor (KIT D816V, IC50: 0.27 nM) and PDGFRα (PDGFRα D842V, IC50: 0.24 nM).

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].

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.

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.

1703793-34-3

C26H27FN10

498.57

BLU-285

H2O:Insoluble
Ethanol:3 mg/mL
DMSO:65 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years