Eltanexor (KPT-8602)

製品コードS8397 バッチS839702

印刷

化学情報

Chemical Structure Synonyms ONO-7706，ATG-016 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H10F6N6O
分子量 428.29 CAS No. 1642300-52-4
Solubility (25°C)* 体外 DMSO 86 mg/mL warmed with 50ºC water bath (200.79 mM)
Water ˂1 mg/mL
Ethanol ˂1 mg/mL warmed with 50ºC water bath
* <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 Eltanexor (KPT-8602, ONO-7706，ATG-016) is a second-generation, orally bioavailable XPO1 inhibitor with IC50 values of 20−211 nM in 10 AML lines after 3 days exposure.
in vitro KPT-8602 is a potent inhibitor of AML cells in cell-based viability assays[1]. KPT-8602 inhibits XPO1/cargo interactions and nuclear export, induces apoptosis of primary CLL cells and significantly inhibits proliferation of diffuse large B-cell lymphoma cell lines[2]
in vivo KPT-8602 is orally bioavailable and has similar pharmacokinetic properties to selinexor, but has markedly reduced (approximately 30-fold less) penetration across the blood−brain barrier. Toxicology studies in rats and monkeys indicate that KPT-8602 has a substantially better tolerability profile, probably due to its inability to penetrate into the CNS, with reduced anorexia, malaise and weight loss compared to selinexor. KPT-8602 exhibits superior anti-leukemic activity and better tolerability in the AML PDX models tested, with nearly complete elimination of human AML cells in the AML-CN model. KPT-8602 is minimally toxic to normal hematopoietic stem and progenitor cells[1]. KPT-8602 does not accumulate in plasma after repetitive dosing and prolongs survival in a human leukemia xenograft model of AML[2].

プロトコル(参考用のみ)

細胞アッセイ 細胞株 Human CLL cells
濃度 0-10 μM
反応時間 24 h and 48 h
実験の流れ

MTS assay and annexin-V/PI flow cytometry.
動物実験 動物モデル NOD-SCID-IL2Rcγnull (NSG) mice
投薬量 15 mg/kg
投与方法 by oral gavage

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：

Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression [ Sci Rep, 2023, 13(1):18554] PubMed: 37899423
Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide [ Biomedicines, 2022, 10(9)2145] PubMed: 36140245
Prognostic and therapeutic significance of XPO1 in T-cell lymphoma [ Exp Cell Res, 2022, 416(2):113180] PubMed: 35489384
PSEN1-selective gamma-secretase inhibition in combination with kinase or XPO-1 inhibitors effectively targets T cell acute lymphoblastic leukemia [ J Hematol Oncol, 2021, 14(1):97] PubMed: 34167562
Targeting XPO1 enhances innate immune response and inhibits KSHV lytic replication during primary infection by nuclear stabilization of the p62 autophagy adaptor protein [ Cell Death Dis, 2021, 12(1):29] PubMed: 33414399
Combining selective inhibitors of nuclear export (SINEs) with chimeric antigen receptor (CAR) T cells for CD19‑positive malignancies [ Oncol Rep, 2021, 46(2)170] PubMed: 34165175
The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia [ Clin Cancer Res, 2020, 10.1158/1078-0432.CCR-20-1315] PubMed: 32826328
Transcriptome Profiling of Acquired Gefitinib Resistant Lung Cancer Cells Reveals Dramatically Changed Transcription Programs and New Treatment Targets [ Front Oncol, 2020, 10:1424] PubMed: 32923394
[ J Hematol Oncol, 2019, ] PubMed: 31752970

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。