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ONO-7475 is a potent 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 provides a bright promise for the study of EGFR-mutated non-small cell lung cancer (NSCLC).
Mice fed a diet containing ONO-7475 exhibited significantly longer survival and, interestingly, blocked leukemia cell infiltration in the liver. In summary, ONO-7475 effectively kills acute myeloid leukemia cells in vitro and in vivo by mechanisms that involve disruption of diverse survival and proliferation pathways.
| Cell Experiment | |
|---|---|
| Cell lines | MOLM13, MV4;11, HL60, OCI-AML3, MOLM13 luc/gfp cells, MOLM13 p53 shRNA cells, BM-MSC |
| Preparation method | 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. |
| Concentrations | 50-500 nM |
| Incubation time | 24 h, 48 h, 72 h |
| Animal Experiment | |
|---|---|
| Animal models | 4-week old female NSG mice bearing MOLM13 cells |
| Formulation | diet containing 0.004% and 0.013% ONO-7475 |
| Dosages | 6 mg/kg, 20 mg/kg |
| Administration | Oral gavage |
| Molecular Weight | 562.57 |
| Formula | C32H26N4O6 |
| CAS Number | 1646839-59-9 |
| Solubility (25°C) | DMSO 100 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related TAM Receptor Products |
|---|
| Bemcentinib
Bemcentinib (R428) is a potent and selective small-molecule inhibitor of Axl kinase with IC50 of 14 nM. |
| SGI-7079
SGI-7079 is a novel Axl inhibitor. |
| UNC2250
UNC2250 is a potent and selective Mer inhibitor with IC50 of 1.7 nM, about 160- and 60-fold selectivity over the closely related kinases Axl/Tyro3. |
| UNC2881
UNC2881 is a specific Mer tyrosine kinase inhibitor with IC50 of 4.3 nM, about 83- and 58-fold selectivity over Axl and Tyro3, respectively |
| Dubermatinib
Dubermatinib (TP-0903) is a potent and selective AXL inhibitor with an IC50 value of 27 nM. |
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