PROTAC SMARCA2/4-degrader-22

SMARCA2 degrader-14 (compound I-408) is a PROTAC degrader targeting both SMARCA2 and SMARCA4. In A549 cells, it achieves degradation of SMARCA2/4 proteins with DC50s less than 100 nM and a maximal degradation rate (Dmax%) exceeding 90% after a 24-hour treatment.

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=CC=C(C=C7)C8=C(C)N=CS8)=O)C[C@@H](OC(C)=O)C6)C(C)(C)C)=O)CC5)C=C(N=N1)C9=C(O)C=CC=C9