Folate-MS432 degrades MEK1/2 in a FOLR1-dependent manner. (A) Schematic illustration of the activation of folate-MS432 by endogenous hydrolase. (B) Western blot analysis of MEK1 and MEK2 levels in HT-29 cells treated with indicated doses of MS432, folate-MS432, or folate-MS432N for 12 h. (C, D) Western blot analysis of MEK1 and MEK2 levels in HT-29 cells after the cotreatment with free folic acid or VHL ligand (VH-032) and 100 nM folate-MS432 for 12 h. (E) Western blot analysis of MEK1 and MEK2 levels in HT-29 cells after the cotreatment with 10 μM MG132 or 1 μM MLN4924 and 100 nM folate-MS432 for 12 h. (F) Cell viability of HT-29 cells after treatment with MS432, folate-MS432, or folate-MS432N for 72 h.