Avapritinib

Catalog No.S8553 Batch:S855305

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Technical Data

Formula

C26H27FN10
Molecular Weight 498.56 CAS No. 1703793-34-3
Solubility (25°C)* In vitro DMSO 100 mg/mL (200.57 mM)
Ethanol 2 mg/mL (4.01 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
2%DMSO 40%PEG300 2%Tween80 56%ddH2O
4.0mg/ml Taking the 1 mL working solution as an example, add 20 μL of 200 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 560 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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

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].
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].

Protocol (from reference)

Animal Study:

[1]
  • Animal Models

    mice

  • Dosages

    10 or 30 mg/kg

  • Administration

    oral

Selleck's Avapritinib has been cited by 13 publications

PDGFRA K385 mutants in myxoid glioneuronal tumors promote receptor dimerization and oncogenic signaling [ Sci Rep, 2024, 14(1):7204] PubMed: 38532028
Avapritinib Carries the Risk of Drug Interaction via Inhibition of UDP-Glucuronyltransferase (UGT) 1A1 [ Curr Drug Metab, 2024, 25(3):197-204] PubMed: 38803186
CRISPR/Cas9-engineering of HMC-1.2 cells renders a human mast cell line with a single D816V-KIT mutation: An improved preclinical model for research on mastocytosis [ Front Immunol, 2023, 14:1078958] PubMed: 37025992
Chinese Pedigree with Hereditary Gastrointestinal Stromal Tumors: A Case Report and Literature Review [ Int J Mol Sci, 2023, 24(1)830] PubMed: 36614290
Antineoplastic efficacy profiles of avapritinib and nintedanib in KIT D816V+ systemic mastocytosis: a preclinical study [ Am J Cancer Res, 2023, 13(2):355-378] PubMed: 36895976
Screening of ETO2-GLIS2-induced Super Enhancers identifies targetable cooperative dependencies in acute megakaryoblastic leukemia [ Sci Adv, 2022, 8(6):eabg9455] PubMed: 35138899
Targeting fibroblast growth factor receptors to combat aggressive ependymoma [ Acta Neuropathol, 2021, 10.1007/s00401-021-02327-x] PubMed: 34046693
Identification of Wee1 as target in combination with avapritinib for Gastrointestinal Stromal Tumor treatment [ JCI Insight, 2020, 143474] PubMed: 33320833
A Novel Kindred with Familial Gastrointestinal Stromal Tumors Caused by a Rare KIT Germline Mutation (N655K): Clinico-Pathological Presentation and TKI Sensitivity [ J Pers Med, 2020, 10(4)E234] PubMed: 33212994
Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants. [ Cancer Cell, 2019, 35(5):738-751] PubMed: 31085175

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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