Limertinib

Limertinib is a covalent inhibitor of mutant EGFR.¹ It is selective for EGFR^L858R/T790M, EGFR^T790M, and EGFR containing an exon 19 deletion (IC₅₀s = 0.3, 0.5, and 0.5 nM, respectively) over wild-type EGFR (IC₅₀ = 6 nM) and a panel of 258 kinases at 100 nM. Limertinib also inhibits Bruton’s tyrosine kinase (BTK) and IL-2-inducible T cell kinase (Itk; IC₅₀s = 2.1 and 0.4 nM, respectively).² It selectively inhibits the proliferation of H1975, PC-9, and HCC827 cancer cells, which express mutant EGFRs (IC₅₀s = 12, 6, and 2 nM, respectively), over A431, LoVo, and A549 cancer cells, which express wild-type EGFR (IC₅₀s = 388, 1,916, and 1,541 nM, respectively). Limertinib (1 mg/kg) induces tumor regression in an H1975 non-small cell lung cancer (NSCLC) mouse xenograft model.¹ Formulations containing limertinib have been used in the treatment of NSCLC.

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1. Zhang, T., Qu, R., Chan, S., et al. Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance. Mol. Cancer 19(1), 90 (2020).

2. Song, P., Bai, G., Chan, S., et al. ASK120067 potently suppresses B-cell or T-cell malignancies in vitro and in vivo by inhibiting BTK and ITK. Front. Pharmacol. 13, 1071114 (2022).