Home Protein Tyrosine Kinase Axl inhibitor - Mertk inhibitor Tamnorzatinib (ONO-7475) For research use only.

Tamnorzatinib (ONO-7475)

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.

Tamnorzatinib (ONO-7475) Chemical Structure

Tamnorzatinib (ONO-7475) Chemical Structure

CAS No. 1646839-59-9

Purity & Quality Control

Batch: S893301 DMSO]100 mg/mL]false]Water]Insoluble]false]Ethanol]Insoluble]false Purity: 99.38%
99.38

Tamnorzatinib (ONO-7475) Related Products

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
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]
Cell Research 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.
In Vivo
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]
Animal Research Animal Models 4-week old female NSG mice bearing MOLM13 cells
Dosages 6 mg/kg, 20 mg/kg
Administration Oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03176277 Terminated
Acute Leukemia|Myelodysplastic Syndromes
Ono Pharmaceutical Co. Ltd
 June 26 2017 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 562.57 Formula

C32H26N4O6
CAS No. 1646839-59-9 SDF --
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
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 100 mg/mL ( (177.75 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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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.

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