Tamnorzatinib (ONO-7475)

製品コードS8933 バッチS893301

印刷

化学情報

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

C32H26N4O6
分子量 562.57 CAS No. 1646839-59-9
Solubility (25°C)* 体外 DMSO 100 mg/mL (177.75 mM)
Water Insoluble
Ethanol 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 Tamnorzatinib (ONO-7475) is a potent, selective, and orally active novel inhibitor of Anexelekto(Axl)/MER tyrosine kinase with IC50 of 0.7 nM and 1.0 nM for AXL and MER, respectively. ONO-7475 suppresses the emergence and maintenance of tolerant cells to the initial EGFR-TKIs, osimertinib or dacomitinib, in AXL-overexpressing EGFR-mutated NSCLC cells. ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells.
in vitro

ONO-7475 is an inhibitor with high specificity for Anexelekto and MER Tyrosine Kinase. ONO-7475 kills or growth arrests FLT3-ITD AML cells. AraC as well as p53 reduction augments ONO-7475-induced apoptosis in MOLM13 cells. Inhibition of AXL suppresses survival and proliferation signaling and induces apoptotic proteins in FLT3-ITD but not WT FLT3 AML cells.[1] ONO-7475 sensitizes AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs osimertinib and dacomitinib. In addition, ONO-7475 suppresses the emergence and maintenance of EGFR-TKI tolerant cells.[2]
in vivo

ONO-7475 is effective in a murine in vivo xenograft model using MOLM13 cells. ONO-7475 prolongs mouse survival and suppresses AML cell infiltration in the liver in the AML xenograft model. ONO-7475 is efficacious for AML therapy and warrants pursuit for development of the drug in the clinic.[1] In the xenograft models of AXL-overexpressing EGFR mutated lung cancer treated with initial combination therapy of ONO-7475 and osimertinib markedly regresses tumors and delays tumor re-growth.[2]

プロトコル(参考用のみ)

細胞アッセイ 細胞株 MOLM13, MV4;11, HL60, OCI-AML3, MOLM13 luc/gfp cells, MOLM13 p53 shRNA cells, BM-MSC
濃度 50-500 nM
反応時間 24 h, 48 h, 72 h
実験の流れ

MOLM13 and MV4;11 (FLT3 ITD) and OCI-AML3 (FLT3 WT) cells are incubated with vehicle (0.1% DMSO) or varying doses of ONO-7475 for 48 hours. Viable cell number and apoptosis are measured by flow cytometry.
動物実験 動物モデル 4-week old female NSG mice bearing MOLM13 cells
投薬量 6 mg/kg, 20 mg/kg
投与方法 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：

AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692] PubMed: 38342232
Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors [ JTO Clin Res Rep, 2023, 4(6):100525] PubMed: 37426308

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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