Tamnorzatinib (ONO-7475)

Catalog No.S8933 Batch:S893301

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Technical Data

Formula

C32H26N4O6
Molecular Weight 562.57 CAS No. 1646839-59-9
Solubility (25°C)* In vitro DMSO 100 mg/mL (177.75 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Tamnorzatinib (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 Assay:

[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 Study:

[1]
  • Animal Models

    4-week old female NSG mice bearing MOLM13 cells

  • Dosages

    6 mg/kg, 20 mg/kg

  • Administration

    Oral gavage

Selleck's Tamnorzatinib (ONO-7475) has been cited by 2 publications

AXL signal mediates adaptive resistance to KRAS G12C inhibitors in KRAS G12C-mutant tumor cells [ Cancer Lett, 2024, 587:216692] PubMed: 38342232
Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors [ JTO Clin Res Rep, 2023, 4(6):100525] PubMed: 37426308

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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