ONO-7475

Catalog No.S8933

For research use only.

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.

ONO-7475 Chemical Structure

CAS No. 1646839-59-9

Purity & Quality Control

Choose Selective Axl Inhibitors

Biological Activity

Description 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 [1]
(Cell-free assay)
Mer [1]
(Cell-free assay)
FLT3 [1]
(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.[1] 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.[2]

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.[1] 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.[2]

Protocol (from reference)

Cell Research:

[1]

  • 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
  • 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.

Animal Research:

[1]

  • Animal Models: 4-week old female NSG mice bearing MOLM13 cells
  • Dosages: 6 mg/kg, 20 mg/kg
  • Administration: Oral gavage

Solubility (25°C)

In vitro

DMSO 100 mg/mL
(177.75 mM)
Water Insoluble
Ethanol Insoluble

Chemical Information

Molecular Weight 562.57
Formula

C32H26N4O6

CAS No. 1646839-59-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=CC2=C(C=CN=C2C=C1OC)OC3=CN=C(C=C3)NC(=O)C4=CC5=C(CCCC5=O)N(C4=O)C6=CC=CC=C6

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Molarity Calculator

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03176277 Recruiting Drug: ONO-7475|Drug: ONO-7475 + venetoclax Acute Leukemia|Myelodysplastic Syndromes Ono Pharmaceutical Co. Ltd June 26 2017 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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