Information Avapritinib (BLU-285) is a small molecule kinase inhibitor that potently inhibitsPDGFRα D842Vmutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogousKit (c-Kit)mutation, D816V in Kit (c-Kit) Exon 17 (IC50 = 0.5 nM). Targets PDGFRα (D842V) ; c-Kit (D816V) 0.5 nM; 0.5 nM In vitro BLU-285 is a selective oral inhibitor that targets KIT Exon 17 and PDGFRα D842 activation loop mutants. Cellular assays measuring inhibition of KIT mutant autophosphorylation confirm the activity of BLU-285 against the KIT D816 mutants D816V (HMC1.2 cells, IC50 = 3 nM) and D816Y (P815 cells, IC50 = 22 nM) as well as other KIT Exon 17 mutants such as N822K (Kasumi cells, IC50 = 40 nM) found in treatment-refractory GIST. In vivo BLU-285 is a well-tolerated, orally bioavailable agent that achieves dose dependent tumor growth inhibition in a D816Y-driven xenograft model. A PK-PD-efficacy relationship with BLU-285 has been established demonstrating that tumor regression results from >90% target suppression and is observed with 30 mg/kg once daily dosing. With potent activity against PDGFRα D842V and KIT Exon 17 mutants, BLU-285 targets previously unaddressed genomic drivers of disease and provides promise for the treatment of PDGFRα D842V-driven GIST(gastrointestinal stromal tumor) or SM(systemic mastocytosis), where more than 90% of patients carry the KIT D816V mutation. Besides single agent activity, the highly selective BLU-285 offers an opportunity for combination with other agents in GIST to cover the entirety of KIT primary and resistance mutants.
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Avapritinib (BLU-285)
CAS number：1703793-34-3 molecular formula：C26H27FN10
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| Chinese alias | - | ||
| English alias | (1S)-1-(4-FLUOROPHENYL)-1-(2-(4-(6-(1-METHYL-1H-PYRAZOL-4-YL)PYRROLO(2,1-F)(1,2,4)TRIAZIN-4-YL)PIPERAZIN-1-YL)PYRIMIDIN-5-YL)ETHAN-1-AMINE | Ayvakit | US10807985, Compound 44 | (1S)-1-(4-fluorophenyl)-1-[2-[4-[6-(1-methylpyrazol-4-yl)pyrrolo[2,1-f][1,2,4] | ||
| CAS number | 1703793-34-3 | molecular formula | C26H27FN10 |
| molecular weight | 498.56 g/mol | Exact mass | - |
| PSA | 106.000 Ų | logp | 1.9 |
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