Avapritinib Chemical Properties

Density 

1.42±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO:83.11(Max Conc. mg/mL);166.7(Max Conc. mM)

form 

A crystalline solid

pka

6.96±0.10(Predicted)

color 

White to light yellow

InChIKey

DWYRIWUZIJHQKQ-JKXWNSIXNA-N

SMILES

C1N(C2N=CC([C@@](N)(C3C=CC(F)=CC=3)C)=CN=2)CCN(C2C3=CC(C4C=NN(C)C=4)=CN3N=CN=2)C1 |&1:6,r|

CAS DataBase Reference

1703793-34-3

Avapritinib Usage And Synthesis

Description

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 KIT^D816V and PDGFRα^D842V, respectively). It is >150-fold selective for KIT^D816V and PDGFRα^D842V 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 KIT^D814Y 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.

Uses

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.

Indications

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).

brand name

Ayvakit

General Description

Class: receptor tyrosine kinase; Treatment: GIST, SM; Other name: BLU-285; Elimination half-life = 32–57 h; Protein binding = 98.8%

Synthesis

Bromide 213 was coupled with pyrazole boronate 214 to give triazone 215. Triazone 215 was converted to the corresponding chloride using phosphorus oxychloride and base in hot toluene. This chloride was smoothly coupled with piperazine 212 under basic conditions in dichloromethane to give avapritinib in high yield.

target

Primary targets: PDGFRA, KIT

References

[1] ERICA K. EVANS. A precision therapy against cancers driven by KIT/PDGFRA mutations[J]. Science Translational Medicine, 2017, 9 414. DOI: 10.1126/scitranslmed.aao1690

Avapritinib(1703793-34-3)Related Product Information

• Pralsetinib
• BLU 9931
• BLU-945
• BLU-782