BLU-285 is a dual inhibitor of KIT receptor and platelet-derived growth factor receptor α (PDGFRα) tyrosine kinases with activating loop mutations (IC50s = 0.27 and 0.24 nM for KITD816V and PDGFRαD842V, respectively). It is >150-fold selective for KITD816V and PDGFRαD842V over a kinase panel at a concentration of 3 μM. BLU-285 also has activity against a panel of KIT and PDGFRα loop mutants identified in patients with gastrointestinal stromal tumors (GISTs; IC50s = <100 nM). It inhibits growth of cancer cell lines containing wild-type and mutant KIT and PDGFRα, demonstrating increased potency in cell lines expressing KIT and PDGFRα with activating loop mutations. 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.
Avapritinib is a medication used for the treatment of tumors due to one specific rare mutation. Avapritinib is a potent, selective, and orally active KIT and PDGFRA activation loop mutant kinases inhibitor.
Avapritinib is approved for the treatment of adult patients with unresectable or metastatic gastrointestinal mesenchymal stromal tumour (GIST) carrying platelet-derived growth factor receptor A (PDGFRA) exon 18 mutations, including the D842V mutation, as well as adult patients with advanced systemic mastocytosis (ASM).
Class: receptor tyrosine kinase;
Treatment: GIST, SM;
Other name: BLU-285;
Elimination half-life = 32–57 h;
Protein binding = 98.8%
Primary targets: PDGFRA, KIT
