Avapritinib

製品コードS8553 バッチS855305

印刷

化学情報

Chemical Structure Synonyms BLU-285 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C26H27FN10
分子量 498.56 CAS No. 1703793-34-3
Solubility (25°C)* 体外 DMSO 100 mg/mL (200.57 mM)
Ethanol 2 mg/mL (4.01 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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).
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].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HMC1.2 cells
濃度 0.5 nM (PDGFRα D842V)
反応時間
実験の流れ

Cells were treated with various concentrations of BLU-285.
動物実験 動物モデル mice
投薬量 10 or 30 mg/kg
投与方法 oral

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Inhibition of the mutated c-KIT kinase in AML1-ETO-positive leukemia cells restores sensitivity to PARP inhibitor. [ Blood Adv, 2019, 3(23):4050-4054] PubMed: 31816060
Avapritinib: A Selective Inhibitor of KIT and PDGFRα that Reverses ABCB1 and ABCG2-Mediated Multidrug Resistance in Cancer Cell Lines [ Mol Pharm, 2019, 16(7):3040-3052] PubMed: 31117741

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。