ONO-7475 (C007B-397890)

InformationONO-7475 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.TargetsAxl (Cell-free assay); Mer (Cell-free assay); FLT3 (Cell-free assay) 0.7 nM; 1.0 nM; 147 nMIn vitroONO-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. 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.In vivoONO-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. 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.Cell Research(from reference)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. Specification: 0.98 Molecular Formula: C32H26N4O6 Molecular Weight: 562.57 PubChem CID: 90645873 Isomeric 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 Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/O414277-SCI_b816858a392deec93c2a451dd5825a42.pdf