MS 39

MS 39 is a highly effective, highly affinity and selective depressant of mutant epidermal growth factor receptor (EGFR) with high efficiency, high affinity and selectivity. MS 39, conjured by gefitinib to VHL ligand via a linker, effectively induced the degradation of mutant EGFR (DC50 values in HCC827 (exon 19 del) and H3255 (L858R mutation) lung cancer cell lines were 5 nM and 3.3 nM, respectively) . However, there was no significant effect in wild-type EGFR cell lines with concentrations up to 10 μM. MS 39 inhibited the proliferation of H3255 lung cancer cells in vitro and was bioavailable in mice after administration.

N(C=1C2=C(C=C(OC)C(OCCCN3CCN(C(CCCCCCCCCC(N[C@H](C(=O)N4[C@H](C(NCC5=CC=C(C=C5)C=6SC=NC6C)=O)C[C@@H](O)C4)[C@@](C)(C)C)=O)=O)CC3)=C2)N=CN1)C7=CC(Cl)=C(F)C=C7