Almonertinib

Almonertinib is an inhibitor of mutant and wild-type EGFR (IC₅₀s = 0.18 and 2.6 nM for EGFR^L858R/T790M and wild-type EGFR, respectively, in a cell-free assay).¹ It is selective for mutant EGFR^D761Y, EGFR^L747S, and EGFR^L861Q (IC₅₀s = 0.84, 3.09, and 1.07 nM, respectively) over EGFR containing mutations at the G719 residue, EGFR^G719C, EGFR^G719D, and EGFR^G719S (IC₅₀s = 17.25, 54.14, and 82.8 nM, respectively).² Almonertinib (100 nM) decreases proliferation and induces apoptosis in patient-derived non-small cell lung cancer (NSCLC) cells that express EGFR containing the exon 20 insertion mutation H773-V774insNPH. It reduces tumor growth in an H1975 NSCLC mouse xenograft model and a patient-derived xenograft (PDX) mouse model of NSCLC.^1,2 Formulations containing almonertinib have been used in the treatment of NSCLC.

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1. Liu, Q., Luo, Y., Li, Z., et al. Structural modifications on indole and pyrimidine rings of osimertinib lead to high selectivity towards L858R/T790M double mutant enzyme and potent antitumor activity. Bioorg. Med. Chem. 36, 116094 (2021).

2. Shi, C., Zhang, C., Fu, Z., et al. Antitumor activity of aumolertinib, a third-generation EGFR tyrosine kinase inhibitor, in non-small-cell lung cancer harboring uncommon EGFR mutations. Acta Pharm. Sin. B 13(6), 2613-2627 (2023).