Limertinib (ASK120067) is an orally active and highly efficient epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR T790M. Limertinib can be used for studying non-small cell lung cancer.

PC9:6 nM, EGFR (WT):6 nM, H1975 (EGFR T790M):12 nM, HCC827 (sensitive mutation):2 nM, EGFR (T790M):0.5 nM (IC50), EGFR (L858R/T790M):0.3 nM (IC50), EGFR (exon 19 deletion):0.5 nM (IC50)

In an in vitro kinase assay, Limertinib exhibited potent inhibition of EGFR L858R/T790M and EGFR T790M resistance mutants with IC50 values of 0.3 nM and 0.5 nM, respectively, as well as a sensitive mutant with deletion of EGFR exon 19 (IC50 = 0.5 nM). In comparison, Limertinib has an IC50 of 6 nM against wild-type EGFR (EGFRWT). [1]
Limertinib selectively inhibited the proliferation of EGFR-mutant cell lines and exhibited significant antiproliferative activity in non-small cell lung cancer (NSCLC) cells harboring mutant EGFR, with IC50 values of 12 nM, 6 nM, and 2 nM for NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitive mutation), respectively.[1]
In the concentration range of 0.1-100 nM, Limertinib inhibits phosphorylation of EGFR at tyrosine residue 1068 and inhibits phosphorylation of its downstream signaling proteins, AKT and ERK, in NCI-H1975 cells (EGFR L858R/T790M), even at low concentrations of 0.1-1 nM. In addition, it reduced the expression levels of p-EGFR, p-Akt, and p-ERK in EGFR WT A431 cells when Limertinib concentration reached 10-100 nM. [1]

By oral administration (5-20 mg/kg once daily for 21 days), Limertinib significantly slowed down tumor growth with a tumor growth inhibition (TGI) of 85.7%. When administered at a dose of 10 mg/kg, Limertinib significantly reduced tumor growth with a TGI rate of 99.3%, showing similar efficacy to Osimertinib. [1]