EGFRmutant- in-1, A 5-methylpyrimidopyridone derivative are effective selective EGFRL858R T790M C797S mutant inhibitors with IC50 of 27.5 nM, which significantly weakened EGFRWT effect.
MS 154 is a potent and selective cereblon-recruiting Degrader (PROTAC®) of mutant epidermal growth factor receptor (EGFR), comprising a cereblon-binding moiety joined by a linker to gefitinib(Iressa). MS 154 decreases EGFR protein levels, inhibits downstream signaling in and inhibits proliferation of mutantEGFR-bearing lung cancer cells (DC50values are 11 and 25 nM in HCC-827 and H3255 cells, respectively; Dmax> 95% at 50 nM), but not in WT-EGFR-bearing ovarian and lung cancer cells lines. Bioavailable in mice following ip administration.
EGFR-IN-1, an orally active and irreversible selective inhibitor targeting L858R T790M mutantEGFR, exhibits strong antiproliferative and antitumor activity, particularly against H1975 cells and first line mutant HCC827 cells. This compound potently inhibits Gefitinib-resistant EGFR L858R T790M mutations with a 100-fold selectivity over the wild-type EGFR.
JBJ-04-125-02 can inhibit cancer cell proliferation and EGFRL858R T790M C797S signaling. JBJ-04-125-02 has anti-tumor activities. JBJ-04-125-02 is a potent, mutant-selective, allosteric and orally active EGFR inhibitor with an IC50 of 0.26 nM for EGFRL858