ChemicalBook CAS DataBase List 1646839-59-9

1646839-59-9

Name	ONO7475
CAS	1646839-59-9
Molecular Formula	C32H26N4O6
MDL Number	MFCD32689448
Molecular Weight	562.57
MOL File	1646839-59-9.mol

Chemical Properties

Boiling point	804.0±65.0 °C(Predicted)
density	1.43±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml
form	A crystalline solid
pka	8.50±0.20(Predicted)
color	Light yellow to yellow

Hazard Information

Uses

Tamnorzatinib (ONO-7475) is a potent, selective, and orally active Axl/Mer inhibitor with IC50 values of 0.7 nM and 1.0 nM, respectively. Tamnorzatinib sensitizes AXL-overexpressing EGFR-mutant NSCLC cells to the EGFR-TKIs, suppresses the emergence and maintenance of tolerant cells. Tamnorzatinib combines with Osimertinib (HY-15772) provides a bright promise for the study of EGFR-mutated non-small cell lung cancer (NSCLC).

in vivo

Tamnorzatinib (oral gavage; 10 mg/kg or combines with 5 mg/kg Osimertinib; 29 days) treatment alone has little effect on the tumor growth. Besides, Osimertinib alone causes tumor regression within one week, but the tumors reappear within three weeks. The combined initial treatment causes tumor regression and the size of tumors is maintained for 4 weeks. No apparent adverse events, including weight loss are observed during these treatments^[1].

Animal Model:	Mouse CDX model using high-AXL-expressing PC-9KGR cells (exon 19 deletion and the exon21-T790M mutation in EGFR)^[1]
Dosage:	10 mg/kg; once daily; 19 days
Administration:	oral gavage
Result:	Had little effects alone, but combined treatments significantly decreased tumor volume without reappear.

IC 50

TrkA; Axl; Tyro3; Mer

References

[1] Okura N, et al. ONO-7475, a Novel AXL Inhibitor, Suppresses the Adaptive Resistance to Initial EGFR-TKI Treatment in?EGFR-Mutated Non-Small Lung Cancer.Clin Cancer Res.?2020 Jan 17. DOI:10.1158/1078-0432.CCR-19-2321
[2] Ruvolo PP, et al. 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.Haematologica.?2017 Dec;102(12):2048-2057. DOI:10.3324/haematol.2017.168856

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