Description
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. MS 154 decreases EGFR protein levels, inhibits downstream signaling in and inhibits proliferation of mutant EGFR-bearing lung cancer cells (DC50 values 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. It is bioavailable in mice following ip administration.
