ONO-7475

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

ONO-7475  纯度: 99.38%

ONO-7475 是一种有效的、选择性的、具有口服活性的 Axl/Mer 抑制剂，IC50 值分别为 0.7 nM 和 1.0 nM。ONO-7475 使 AXL 过表达的 EGFR 突变型 NSCLC 细胞对 EGFR-TKIs 敏感，抑制耐药细胞的产生和耐药性的维持。ONO-7475 联合 Osimertinib (HY-15772) 为 EGFR 突变非小细胞肺癌 (NSCLC) 的研究提供了一个光明的前景。

ONO-7475

ONO-7475 Chemical Structure

CAS No. : 1646839-59-9

规格 价格 是否有货 数量
Free Sample (0.1-0.5 mg)   Apply now  
10 mM * 1 mL in DMSO ￥3090 In-stock
5 mg ￥2500 In-stock
10 mg ￥3500 In-stock
50 mg ￥7800 In-stock
100 mg   询价  
200 mg   询价  

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ONO-7475 相关产品

•相关化合物库:

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生物活性

ONO-7475 is a potent, selective, and orally active Axl/Mer inhibitor with IC50 values of 0.7 nM and 1.0 nM, respectively. ONO-7475 sensitizes AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs, suppresses the emergence and maintenance of tolerant cells. ONO-7475 combines with Osimertinib (HY-15772) provides a bright promise for the study of EGFR-mutated non-small cell lung cancer (NSCLC)[1].

IC50 & Target

IC50: 0.7 nM (AXL)[1]
IC50: 1.0 nM (MER tyrosine kinase)[2]
体外研究
(In Vitro)

ONO-7475 is against recombinant human AXL with IC50 values of 0.414 nM and 0.7 nM in off-chip MSA and ACD cell-based tyrosine kinase assay, respectively. It is against AXL, MER, TYRO3, TRKB, PDGFR alpha, TRKA, and FLT3 activities with IC50 values of 0.7 nM, 1.0 nM, 8.7 nM, 15.8 nM, 28.9 nM, 35.7 nM and 147 nM, respectively in a Cell-based Tyrosine Kinase assay[2].
ONO-7475 (0.0001 μM-1 μM; 72 hours) increases the sensitivity to Osimertinib and Dacomitinib and reduces the viability of high AXL-expressing PC-9 and HCC4011 cells, but not of low-AXL-expressing HCC827 cells. Besides, ONO-7475 enhances Osimertinib efficacy on the viability of cell lines PC-9, PC-9KGR, and HCC4011, and H1975, all of which express high levels of AXL. But it has a marginal effect on the viability of cell lines HCC827, HCC4006, and H3255 with low levels of AXL[1].
ONO-7475 (1 μM; 4 or 48 hours) combines with Osimertinib markedly inhibits the phosphorylation of AXL, AKT, and p70S6K compared with the treatment of the high-AXL-expressing cell lines treated with Osimertinib alone at 4 hours. It combines with osimertinib increases cleaved PARP in PC-9 and HCC4011 cells compared with the treatment with Osimertinib alone[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Viability Assay[1]

Cell Line: High AXL-expressing cell: PC-9,HCC4011,H1975, PC-9KGR cells
Low AXL-expressing cell: HCC827, HCC4006, and H3255 cells
Concentration: 0.0001 μM; 0.001 μM; 0.01 μM; 0.1 μM; 1 μM
Incubation Time: 72 hours
Result: Increased the sensitivity and efficacy to Osimertinib in AXL-high level cells.

Western Blot Analysis[1]

Cell Line: PC-9, HCC4011 cells
Concentration: 1 μM
Incubation Time: 4 or 48 hours
Result: Increased p-AXL, AKT, and p70S6K expression at 4 hours and increases p-PARP expression at 48 hours when combindes with Osimertinib.

体内研究
(In Vivo)

ONO-7475 (oral gavage; 10 mg/kg or combines with 5 mg/kg Osimertinib; 29 days) treatment alone has little effect on the tumor growth. Besides, Osimertinib alone causes tumor regression within one week, but the tumors reappear within three weeks. The combined initial treatment causes tumor regression and the size of tumors is maintained for 4 weeks. No apparent adverse events, including weight loss are observed during these treatments[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Mouse CDX model using high-AXL-expressing PC-9KGR cells (exon 19 deletion and the exon21-T790M mutation in EGFR)[1]
Dosage: 10 mg/kg; once daily; 19 days
Administration: oral gavage
Result: Had little effects alone, but combined treatments significantly decreased tumor volume without reappear.

Clinical Trial

分子量

562.57

Formula

C32H26N4O6
CAS 号

1646839-59-9
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 250 mg/mL (444.39 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.7776 mL 8.8878 mL 17.7756 mL
5 mM 0.3555 mL 1.7776 mL 3.5551 mL
10 mM 0.1778 mL 0.8888 mL 1.7776 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。
参考文献

  • [1]. Okura N, et al. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in EGFR-Mutated Non-Small Lung Cancer.Clin Cancer Res. 2020 Jan 17.

    [2]. Ruvolo PP, et al. Anexelekto/MER tyrosine kinase inhibitor ONO-7475 arrests growth and kills FMS-like tyrosine kinase 3-internal tandem duplication mutant acute myeloid leukemia cells by diverse mechanisms.Haematologica. 2017 Dec;102(12):2048-2057.

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