limertinib

limertinib (ASK120067) is a potent and orally active inhibitor of EGFR T790M ( IC 50 :0.3 nM) with selectivity over EGFR WT (IC 50 :6.0 nM). limertinib is a third-generation EGFR-TKI for the research of non-small cell lung cancer (NSCLC) In Vitro In the in vitro kinase assay limertinib potently inhibits the EGFR L858R/T790M and EGFR T790M resistant mutants with IC 50 values of 0.3 nM and 0.5 nM, respectively, as well as the EGFR exon19 del sensitizing mutant (IC 50 = 0.5 nM). The 50 of limertinib against wild-type EGFR (EGFR WT ) is 6 nM. limertinib selectively inhibits the growth of EGFR-mutant cell lines and exhibits potent antiproliferative activity in the mutant EGFR NSCLC cells, with IC 50 values of 12 nM, 6 nM and 2 nM against NCI-H1975 (T790M mutation), PC-9, and HCC827 cells (sensitizing mutations), respectively. However, it shows moderate or weak anti-growth activities in A431, LoVo and A549 cells (EGFR WT ), with IC 50 values ranging from 338 nM to 1541 nM. limertinib (0.1-100 nM) inhibits the phosphorylation of EGFR at Tyrosine residue 1068 and its downstream signaling proteins AKT and ERK in NCI-H1975 cells (EGFR L858R/T790M ) even at low dosage (0.1-1 nM). Additionally, limertinib inhibits p-EGFR and p-Akt and p-erk in EGFR WT A431 cell until the concentration reaches 10 to 100 nM. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo limertinib (oral gavage; 5-20 mg/kg; once daily; 21 days) results in significantly regressed tumor growth, with a tumor growth inhibition (TGI) rate of 85.7%, and administration of 10 mg/kg limertinib causes dramatic tumor shrinkage with a TGI rate of 99.3%, exhibiting a similar potency with Osimertinib . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: BALB/cA nude mice Dosage: 5-20 mg/kg Administration: Oral gavage; 5-20 mg/kg; once daily; 21 days Result: Were well tolerated in animals without observed body weight loss Demonstrated profound and selective antitumor efficacy and decreased TGI rate. Significantly inhibited the phosphorylation of EGFR L858R/T790M and AKT in tumor tissue. Form:Solid IC50& Target:EGFR T790M 0.5 nM (IC 50 ) EGFR L858R/T790M 0.3 nM (IC 50 ) EGFR (WT) 6 nM (IC 50 ) EGFR Exon 19 deletion 0.5 nM (IC 50 )

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