Home Protein Tyrosine Kinase PDGFR inhibitor - c-Kit inhibitor Avapritinib For research use only.

Avapritinib

Synonyms: BLU-285

Avapritinib is a small molecule kinase inhibitor that potently inhibits PDGFRα D842V mutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogous Kit (c-Kit) mutation, D816V in Kit (c-Kit) Exon 17 (IC50 = 0.5 nM).

Avapritinib Chemical Structure

Avapritinib Chemical Structure

CAS No. 1703793-34-3

Purity & Quality Control

Avapritinib Related Products

Signaling Pathway

PDGFR Signaling Pathways

PDGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit D816V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.008 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of PDGFRalpha V561D/D842V mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.01 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.017 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and D820A mutant and D820A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.019 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of TEL-fused PDGFRbeta (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.022 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and A829P mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.028 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit V560D/D816H mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.029 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of TEL-fused PDGFRalpha (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and N822K mutant and Y823D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.034 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit V560D mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.042 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 9 AY502 to 503 insertion and D816 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.069 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.078 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (560 to 578 residues) mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.117 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 9 AY502 to 503 insertion mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.167 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.292 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit V560D/V654A mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.427 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 9 AY502 to 503 insertion and V654 mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.751 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of Kit exon 11 deletion (557 to 558 residues) and D816H mutant and T670I mutant (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 0.86 μM. 30204441
BA/F3 cells Cytotoxicity assay 72 h Cytotoxicity in mouse parental BA/F3 cells incubated for 72 hrs by MTS assay, GI50 = 4.075 μM. 30204441
BA/F3 cells Growth inhibiton assay 72 h Inhibition of KDR (unknown origin) transfected in mouse BA/F3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTS assay, GI50 = 4.952 μM. 30204441
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Biological Activity

Description Avapritinib is a small molecule kinase inhibitor that potently inhibits PDGFRα D842V mutant activity in vitro (IC50 = 0.5 nM) and PDGFRα D842V autophosphorylation in the cellular setting (IC50 = 30 nM); also a potent inhibitor of the analogous Kit (c-Kit) mutation, D816V in Kit (c-Kit) Exon 17 (IC50 = 0.5 nM).
Targets
PDGFRα (D842V) [1] c-Kit (D816V) [1]
0.5 nM 0.5 nM
In vitro
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[1].
Experimental Result Images Methods Biomarkers Images PMID
Western blot PDGFRA / c-KIT / Wee1 / Cdc2 / PARP / γH2AX / CyclinD1 / β-actin 33320833
In Vivo
In vivo

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[1].
Animal Research Animal Models mice
Dosages 10 or 30 mg/kg
Administration oral
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04908176 Completed
Gastrointestinal Stromal Tumors|GIST|Non-resectable Advanced Solid Tumors|Recurrent or Unresectable Central Nervous System (CNS) Tumors
Blueprint Medicines Corporation
 August 24 2022 Phase 1
NCT04695431 Completed
Advanced Systemic Mastocytosis|Aggressive Systemic Mastocytosis|Systemic Mastocytosis With an Associated Hematological Neoplasm|Mast Cell Leukemia
Blueprint Medicines Corporation|Analysis Group Inc.
 December 2 2020 --
NCT03731260 Active not recruiting
Indolent Systemic Mastocytosis
Blueprint Medicines Corporation
 April 16 2019 Phase 2
NCT03580655 Active not recruiting
Advanced Systemic Mastocytosis|Aggressive Systemic Mastocytosis|Systemic Mastocytosis With an Associated Hematologic Neoplasm|Mast Cell Leukemia
Blueprint Medicines Corporation
 November 21 2018 Phase 2
NCT03465722 Completed
GIST
Blueprint Medicines Corporation
 March 26 2018 Phase 3

Chemical Information & Solubility

Molecular Weight 498.56 Formula

C26H27FN10
CAS No. 1703793-34-3 SDF Download Avapritinib SDF
Smiles CC(C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (200.57 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 1.5 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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