Avapritinib (BLU-285) is a selective, highly potent, and orally active inhibitor of KIT and PDGFRA activation loop mutant kinases, targeting KIT D816V (IC50:0.27 nM) and PDGFRA D842V (IC50:0.24 nM), and attenuates the transport functions of ABCB1 and ABCG2. It binds to the active conformation of the kinases and exhibits antitumor activity.

PDGFRα (D842V):0.24 nM, c-Kit (D816V):0.27 nM

Avapritinib (BLU-285) 已证明对 KIT 外显子 17 突变酶 KIT D816V 具有生化体外活性， IC50值为0.27 nM；通过在人肥大细胞白血病细胞系 HMC1.2 和 P815 小鼠肥大细胞瘤细胞系中自磷酸化来测量 KIT D816 突变体上 BLU-285 的细胞活性，IC50分别为4 和 22 nM。[1]

方法：在注射后潜伏期21天后，小鼠口服给药Avapritinib (BLU-285)，每天一次，剂量为10mg / kg或30mg / kg，直至第45天,采用Kasumi-1 luc+ AML NOG SCID 小鼠股骨注射模型评估 Avapritinib (BLU-285) 在 KIT 外显子 17 突变 CBF-AML 中的疗效。
结果：两种剂量（10 或 30 mg/kg，口服，每日一次）的 Avapritinib (BLU-285) 在整个研究中显着减轻了疾病负担。10 或 30 mg/kg 的 Avapritinib (BLU-285)导致所有动物的肿瘤消退。[1]

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.