C199

C199 is a PROTAC degrader targeting PRMT4 (DC50 = 106 nM). C199 shows high selectivity for PRMT4 over other protein arginile methyltransferases. C199 exhibits strong cell degradation ability. C199 induces apoptosis in MM cell lines. C199 efficiently clears PRMT4 protein via the VHL-proteasome pathway. C199 has a relatively long half-life and shows strong anti-multiple myeloma (MM) tumor activity (Pink: Target protein ligand ; Blue: E3 ligase ligand (HY-112078), E3 ligase ligand + linker (HY-174474) ; black: Linker).

C67H95ClN10O8S

1236.05

O=C(N[C@H](C1=CC=C(C=C1)C2=C(N=CS2)C)C)[C@H]3N(C[C@@H](C3)O)C([C@H](C(C)(C)C)NC(CCCCCCCCCCCCCCCC(N4CCC5(CN(C5)C6=NC(C7=CC(OC[C@@H](CNC)O)=CC=C7Cl)=NC(C8=C(ON=C8C)C)=C6C)CC4)=O)=O)=O

Apoptosis; Histone Methyltransferase; PROTACs

PRMT4; von Hippel-Lindau (VHL)

Room temperature