PROTAC EGFR Degrader 9

A PROTAC that drives mutant EGFR degradation, selectively induces degradation of mutant EGFRs over wild-type EGFR (DC50s = 10.2, 36.5, 88.5, 75.4, and >300 nM for EGFRL858R/T790M/C797S, EGFRDelta19/T790M/C797S, EGFRL858R/T790M, EGFRDelta19, and wild-type EGFR, respectively), inhibits the growth of H1975 cells expressing mutant EGFRL858R/T790M/C797S (IC50 = 10.3 nM) and induces cell cycle arrest at the G0/G1 phase and apoptosis in the same cells, reduces tumor size in H1975 xenograft mouse model at 25 and 100 mg/kg. SMILES: FC(F)(F)C(C(C(C1=CC=CC=C12)=CN2[S](CC)(=O)=O)=N3)=CN=C3NC4=CC=C(N(CC5)CCN5CCCCCCC(NC6=C(CN(C(CCC7=O)C(N7)=O)C8=O)C8=CC=C6)=O)C=C4. InChi Code: InChI=1S/C45H48F3N9O6S/c1-2-64(62,63)57-28-34(31-10-6-7-13-37(31)57)41-35(45(46,47)48)26-49-44(53-41)50-29-15-17-30(18-16-29)55-24-22-54(23-25-55)21-8-4-3-5-14-39(58)51-36-12-9-11-32-33(36)27-56(43(32)61)38-19-20-40(59)52-42(38)60/h6-7,9-13,15-18,26,28,38H,2-5,8,14,19-25,27H2,1H3,(H,51,58)(H,49,50,53)(H,52,59,60). InChi Key: NFLKKMOHWZTOPF-UHFFFAOYSA-N