Zorifertinib

EGFR (exon 19 deletion):0.2 nM|EGFR (L858R):0.2nM|TK (WT):0.3nM

AZD3759 shows good oral bioavailability in dogs, and penetrates extensively into monkey brain. In a brain metastasis PC-9 (Exon19Del) model, AZD3759 (15 mg/kg) causes significant dose-dependent antitumor efficacy. [1]

In H3255 (L858R) cells, AZD3759 inhibits EGFR phosphorylation with IC50 of 7.2 nM. AZD3759 demonstrates inhibitory effects on both the pEGFR pathway and cell proliferation of EGFR mutation-derived cells PC-9 and H3255 with IC50 of 7.7 nM and 7 nM, respectively, showing mo activity on cell proliferation of H838 cells. [1]

DMSO:50 mg/mL (108.72 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:18 mg/mL (39.1 mM)

Cell proliferation assay is determined by MTS methods. Briefly, cells are seeded in 96-well plates (at a density to allow for logarithmic growth during the 72-hour assay) and incubated overnight at 37 °C and 5% CO2. Cells are then exposed to concentrations of compounds ranging from 30 to 0.0003 mM for 72 hours. For the MTS endpoint, cell proliferation is measured by the CellTiter AQueous Non-Radioactive Cell Proliferation Assay reagent in accordance with the manufacturer's protocol. Absorbance is measured with a Tecan Ultra instrument. Predose measurements are made, and concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) values are determined using absorbance readings.(Only for Reference)