Information ONO-7475 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. Targets Axl (Cell-free assay); Mer (Cell-free assay); FLT3 (Cell-free assay) 0.7 nM; 1.0 nM; 147 nM 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. 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. 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. 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. Cell Research(from reference) Cell lines：MOLM13, MV4;11, HL60, OCI-AML3, MOLM13 luc/gfp cells, MOLM13 p53 shRNA cells, BM-MSC Concentrations：50-500 nM Incubation Time：24 h, 48 h, 72 h
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ONO-7475
Dangerous GoodsCAS number：1646839-59-9 molecular formula：C32H26N4O6
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| Chinese alias | - | ||
| English alias | 0VCB95RHRV | SCHEMBL16426362 | tamnorzatinib | 1646839-59-9 | N-[5-(6,7-dimethoxyquinolin-4-yl)oxypyridin-2-yl]-2,5-dioxo-1-phenyl-7,8-dihydro-6H-quinoline-3-carboxamide | D81666 | N-(5-((6,7-Dimethoxyquinolin-4-yl)oxy)pyridin-2-yl)-2,5-dioxo-1-phenyl-1,2 | ||
| CAS number | 1646839-59-9 | molecular formula | C32H26N4O6 |
| molecular weight | 562.57 g/mol | Exact mass | - |
| PSA | 120.000 Ų | logp | 3.872 |
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Safety information
pictogram：
GHS07
Signal word：
Warning
Hazard Statement：
H315: 引起皮肤刺激 H319: 引起严重眼睛刺激 H335: 可能引起呼吸道刺激 H302: 吞食有害
Statement of Preventive Measures：
P261: 避免吸入灰尘/烟雾/气体/雾/蒸汽/喷雾 P305+P351+P338: 如进入眼睛：用水小心冲洗几分钟。如戴隐形眼镜并可方便地取出，取出隐形眼镜。继续冲洗。
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