貨號	規格	價格	上海	北京	武漢	南京
S20611-5mg	≥98%	￥1132.00 S20611-5mg ￥1132.00 現貨	6 6	-	-	-
S20611-10mg	≥98%	￥1942.00 S20611-10mg ￥1942.00 現貨	10 10	-	-	-
S20611-25mg	≥98%	￥3777.00 S20611-25mg ￥3777.00 現貨	6 6	-	-	-
S20611-50mg	≥98%	￥7200.00 S20611-50mg ￥7200.00 現貨	6 6	-	-	-

產品介紹

ONO-7475 是一種有效的、選擇性的、具有口服活性的 Axl/Mer 抑制劑，IC50 值分別為 0.7 nM 和 1.0 nM。ONO-7475 使 AXL 過表達的 EGFR 突變型 NSCLC 細胞對 EGFR-TKIs 敏感，抑制耐藥細胞的產生和耐藥性的維持。ONO-7475 聯合 Osimertinib (HY-15772) 為 EGFR 突變非小細胞肺癌 (NSCLC) 的研究提供了一個光明的前景。

產品描述：

靶點：

IC50: 0.7 nM (AXL);IC50: 1.0 nM (MER tyrosine kinase);Trkreceptor;?TAMReceptor

體外研究：

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.
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.
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.

體內研究：

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.

參考文獻：

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.

保存條件：

-20°C

配置溶液濃度參考：

	1mg	5mg	10mg
1 mM	1.778 ml	8.888 ml	17.776 ml
5 mM	0.356 ml	1.778 ml	3.555 ml
10 mM	0.178 ml	0.889 ml	1.778 ml
50 mM	0.036 ml	0.178 ml	0.356 ml

注意：

部分產品我司僅能提供部分信息，我司不保證所提供信息的權威性，僅供客戶參考交流研究之用。

參考文獻

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