Lazertinib (YH25448,GNS-1480)

Lazertinib (formerly known as GNS-1480; YH-25448; GNS1480; YH25448; LECLAZA) is an oral, highly mutant-selective and irreversible 3rd generation EGFR TKI (Tyrosine-kinase inhibitors) approved in 2021 for the treatment of lung cancer (NSCLC). It has 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. Lazertinib is a brain-penetrant EGFR-TKI that spares wild type-EGFR in favor of activating EGFR mutations Ex19del and L858R and targeting the T790M mutation. Lazertinib was approved in January 2021 with the intention of treating patients with EGFR mutations who have locally advanced or metastatic NSCLC. EGFR single and double mutant kinase activity was selectively inhibited by lazertinib, with IC50 values of 2 nM for L858R/T790M and 76 nM for wt-EGFR. The GI50 values for H1975 cells (L858R/T790M), PC9 cells (del19), and H2073 cells (wt) in the cell proliferation assays were 6 nM, 5 nM, and 711 nM, respectively. Lazertinib exhibited a more robust inhibition of cancer cell growth in primary cancer cells from patients with EGFR mutations than osimertinib. When lazertinib was administered once daily at doses ranging from 1 to 25 mg/kg, mice implanted with H1975 cells showed dose-dependent tumor regression in both subcutaneous and intracranial lesions. There were no alterations in body weight or unusual clinical symptoms because of its high selectivity against wild type and broad safety margin. When compared to the same doses of osimertinib, lazertinib produced a more significant, complete inhibition of tumor growth and a longer overall survival at 10–25 mg/kg. Lazertinib treatment effectively inhibited pEGFR expression in tumor tissue in a dose-dependent manner, which was reflected in its in vivo effectiveness. Lazertinib had a 5.9–6.8 hour plasma half-life and a 3.0-5.1 tumor to plasma AUC0-last ratio. Additionally, lazertinib demonstrated remarkable BBB penetration, obtaining CSF concentrations that were higher than the IC50 value for pEGFR inhibition.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.