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 K_i 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-7^EGFR (IC₅₀=0.075 μM), MCF-7^D538G (IC₅₀=0.31 μM), MCF-7^Y537S (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 (HY-163680); Black: linker (HY-W007559); Blue: ligand for E3 ligase (HY-112078))^[1]

1124.30

C₅₈H₆₄F₃N₇O₉S₂

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

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Xin L, et al., Discovery of Novel ERα and Aromatase Dual-Targeting PROTAC Degraders to Overcome Endocrine-Resistant Breast Cancer. J Med Chem. 2024 Jun 13;67(11):8913-8931.  [Content Brief]