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ONO-7475
本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。
ONO-7475图片
CAS NO:1646839-59-9
包装与价格：
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议

产品介绍
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。
生物活性

ONO-7475 is a potent, selective, and orally activeAxl/Merinhibitor withIC50values of 0.7 nM and 1.0 nM, respectively. ONO-7475 sensitizes AXL-overexpressingEGFR-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 lungcancer(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 withIC50values 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 IC50values 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].

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].

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

性状

Solid

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°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 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 mg5 mg10 mg
1 mM1.7776 mL8.8878 mL17.7756 mL
5 mM0.3555 mL1.7776 mL3.5551 mL
10 mM0.1778 mL0.8888 mL1.7776 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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。