Gilteritinib (ASP2215)

製品コードS7754 バッチS775401

印刷

化学情報

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

C29H44N8O3
分子量 552.71 CAS No. 1254053-43-4
Solubility (25°C)* 体外 DMSO 5 mg/mL (9.04 mM)
Ethanol 5 mg/mL (9.04 mM)
Water Insoluble
* <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 Gilteritinib (ASP2215) is a small-molecule FLT3/AXL inhibitor with IC50 values of 0.29 nM and 0.73 nM for FLT3 and AXL, respectively. It inhibits FLT3 at an IC50 value that was approximately 800-fold more potent than the concentration required to inhibit c-KIT (230 nM).
in vitro Gilteritinib demonstrates potent inhibitory activity against the internal tandem duplication (FLT3-ITD) and FLT3-D835Y point mutations in cellular assays using MV4-11 and MOLM-13 cells as well as Ba/F3 cells expressing mutated FLT3. Gilteritinib decreases the phosphorylation levels of FLT3 and its downstream targets in both cellular and animal models. Gilteritinib inhibits the activity of eight of the 78 tested kinases by over 50% at concentrations of either 1 nM (FLT3, LTK, ALK, and AXL) or 5 nM (TRKA, ROS, RET, and MER)[1]. Gilteritinib treatment for 48h results in an induction of apoptosis in MV4-11 cells as determined by an increase in annexin V-positive cells. Gilteritinib also decreases the expression of anti-apoptotic proteins such as MCL-1, BCL2L10, and survivin, which are reported to be important in chemotherapy sensitivity, following 24h treatment[2].
in vivo In vivo, gilteritinib is distributed at high levels in xenografted tumors after oral administration. The decreased FLT3 activity and high intratumor distribution of gilteritinib translates to tumor regression and improved survival in xenograft and intra-bone marrow transplantation models of FLT3-driven AML. This antitumor activity is associated with a durable inhibition of phospho-FLT3 and phospho-STAT5. Furthermore, treatment with gilteritinib decreases the leukemic burden and prolongs survival in a mouse IBMT model. No overt toxicity is seen in mouse models treated with gilteritinib[1].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MV4-11 cells
濃度 0.1 nM, 1 nM, and 10 nM
反応時間 2 h
実験の流れ

MV4-11 cells are treated with DMSO or increasing concentrations of gilteritinib for 2 hours. Immunoprecipitation and immunoblot for phosphorylated FLT3 and total FLT3 are performed.
動物実験 動物モデル MV4-11 xenografted mice (Nude mice)
投薬量 1 mg/kg, 6 mg/kg, and 10 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：

Pharmacological inhibition of RAS overcomes FLT3 inhibitor resistance in FLT3-ITD+ AML through AP-1 and RUNX1 [ iScience, 2024, 27(4):109576] PubMed: 38638836
The impact of an additional copy of chromosome 21 in B-cell precursor acute lymphoblastic leukemia [ Genes Chromosomes Cancer, 2024, 63(1):e23217] PubMed: 38087879
Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks [ Immunity, 2023, 56(8):1778-1793.e10] PubMed: 37463581
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] PubMed: 37726279
A combinatorial therapeutic approach to enhance FLT3-ITD AML treatment [ Cell Rep Med, 2023, 10.1016/j.xcrm.2023.101286] PubMed: 37951217
Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML [ Cell Rep Med, 2023, 4(11):101290] PubMed: 37992684
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia [ Nat Commun, 2023, 14(1):5709] PubMed: 37726279
Transgenic IDH2R172K and IDH2R140Q zebrafish models recapitulated features of human acute myeloid leukemia [ Oncogene, 2023, 42(16):1272-1281] PubMed: 36739363
The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors [ Cell Death Discov, 2023, 9(1):44] PubMed: 36739272
An In Vitro Model for Acute Myeloid Leukemia Relapse Using the SORE6 Reporter [ Int J Mol Sci, 2023, 25(1)496] PubMed: 38203669

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。

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