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ONO-7475

Cat. No. M10497
ONO-7475 Structure
Synonym:

ONO7475

Size Price Availability Quantity
5mg USD 185  USD185 In stock
25mg USD 550  USD550 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

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.

Protocol
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
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information
Molecular Weight 562.57
Formula C32H26N4O6
CAS Number 1646839-59-9
Purity >99%
Solubility DMSO 100 mg/mL
Storage at -20°C
References

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

[2] Peter P Ruvolo, et al. Haematologica. 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

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  Catalog
Abmole Inhibitor Catalog




Keywords: ONO-7475, ONO7475 supplier, Axl, inhibitors

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