Figure 4.
Compound 2c is an effective and persistent IDO1 degrader. (A) Structures of 2c, 2c-CH3, Epa-8PEG and Pom-8PEG. (B) Effect of control compounds on IDO1 degradation. HeLa cells were treated with 5 μmol/L of 2c or control compounds and IFN-γ (5 ng/mL) for 24 h. (C) Confirmation of UPS based mechanism in driving IDO1 degradation upon 2c treatment. HeLa cells were pre-treated with 1 μmol/L of Epa, Pom, MG132 or MLN4924 for 2 h, then 2c (5 μmol/L) and IFN-γ (5 ng/mL) were incubated with HeLa cells for 24 h. (D) and (E) HeLa cells were treated with or without 2c (5 μmol/L) in the presence of IFN-γ (5 ng/mL) for 48 h. Compound 2c leads to efficient and sustained degradation of IDO1.