PROTAC SMARCA2/4-degrader-20

PROTAC SMARCA2/4-degrader-20 (Compound I-405) is a PROTAC degrader targeting the catalytic subunit SMARCA2 in the SWI/SNF complex. It degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM. Additionally, it degrades SMARCA4 in MV411 with a DC50 ranging between 100 to 500 nM.

NC1=C(N2CC3N(C(C2)CC3)C=4N=CC(=CN4)[C@@H]5CC[C@@H](C(N[C@H](C(=O)N6[C@H](C(NCC7=C(OC(F)(F)F)C=C(C=C7)C8=C(C)N=CS8)=O)C[C@@H](O)C6)C(C)(C)C)=O)CC5)C=C(N=N1)C9=C(O)C=CC=C9