Lazertinib (C09-0935-915)

InformationLazertinib (YH25448,GNS-1480) is a potent, highly mutant-selective and irreversibleEGFR-TKIwith IC50 values of 1.7 nM, 2 nM, 5 nM, 20.6 nM and 76 nM for Del19/T790M, L858R/T790M, Del19, L85R and Wild type EGFR respectively, showing much higher IC50 values aganist ErbB2 and ErbB4.TargetsDel19/T790M (Cell-free assay); L858R/T790M EGFR (Cell-free assay); Del19 (Cell-free assay); L85R (Cell-free assay); WT EGFR (Cell-free assay) 1.7 nM; 2 nM; 5 nM; 20.6 nM; 76 nMIn vitroLazertinib targets the activating EGFR mutations Del19 and L858R, as well as the T790M mutation, while sparing wild type. In NSCLC cell lines and primary cancer cells from patients harboring EGFR mutations, YH25448 more potently inhibits cancer cell growth and significantly increases tumor cell apoptosis compared to osimertinib. In the cell proliferation assays, GI50 values of lazertinib are 6 nM, 5 nM, and 711 nM for H1975 cells (L858R/T790M), PC9 cells (del19) and H2073 cells (wt), respectively.In vivoIn an in vivo mouse model implanted with H1975 cells, once-daily YH25448 treatment results in indramatic dose-dependent tumor regression in both subcutaneous and intracranial lesions with no abnormal signs such as skin keratosis. The plasma half-life of YH25448 is 5.9-6.8 hr, while the tumor to plasma AUC0-last ratio is 3.0-5.1 in tumor-bearing mice. YH25448 shows excellent penetration of the blood-brain bartier, achieving CSF concentrations exceeding the IC50 value for pEGFR inhibition. YH25448 shows superior efficacy for tumor regression in an EGFR mutant brain metastasis model.Cell Research(from reference)Cell lines：Ba/F3 cells Concentrations：5, 10, 100 nM Incubation Time：6 h. Specification: 0.98 Molecular Formula: C30H34N8O3 Molecular Weight: 554.64 PubChem CID: 121269225 Isomeric SMILES: CN(C)CC1=CN(N=C1C2=CC=CC=C2)C3=NC(=NC=C3)NC4=C(C=C(C(=C4)NC(=O)C=C)N5CCOCC5)OC Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/L414136-SCI_ec1f635dfb4d297828e5959e444febc0.pdf