PROTAC ERα Degrader-9

PROTAC ERα Degrader-9 (Compound 18c) is a dual-targeting PROTAC degrader, which degrades estrogen receptor α (ERα) and aromatase (ARO). PROTAC ERα Degrader-9 binds to ERα with a Ki of 0.25 μM, inhibits ARO with an IC50 of 4.6 μM. PROTAC ERα Degrader-9 inhibits the proliferation of MCF-7 wildtype (IC50=0.54 μM) and ERα mutants MCF-7EGFR (IC50=0.075 μM), MCF-7D538G (IC50=0.31 μM), MCF-7Y537S (IC50=2.3 μM), downregulates the expressions of ERS1 and MYC. PROTAC ERα Degrader-9 arrests the cell cycle at G2/M, induces apoptosis in MCF-7. PROTAC ERα Degrader-9 exhibits antitumor efficacy in mouse models. (Pink: ligand for target protein ; Black: linker (HY-W007559) ; Blue: ligand for E3 ligase (HY-112078) )

C58H64F3N7O9S2

1124.3

OC1=CC=C(C2=C([C@@H]3C(C[C@H]2O3)S(N(CC(F)(F)F)C4=CC=C(C=C4)OCCCCCC(N[C@H](C(N5[C@@H](C[C@H](C5)O)C(N[C@H](C6=CC=C(C=C6)C7=C(N=CS7)C)C)=O)=O)C(C)(C)C)=O)(=O)=O)C8=CC=C(C=C8)N9C=CN=C9)C=C1

Apoptosis; Cytochrome P450; Estrogen Receptor/ERR; PROTACs

Aromatase/CYP19A1; ERα; ERβ

Room temperature