PROTAC 20S proteasome subunit β5 degrader 2

PROTAC 20S proteasome subunit β5 degrader 2 (compound 14) binds directly to recombinant human 20S proteasome subunit β5 with a K_D value of 1.58 μM; it also binds to recombinant human CRBN with a K_D value of 29.6 μM, indicating that it forms a ternary complex with these two proteins. It induces the formation of a ternary complex consisting of 20S proteasome subunit β5, the degrader itself and CRBN in FaDu cells, thereby mediating the ubiquitination and degradation of the target protein^[1].
PROTAC 20S proteasome subunit β5 degrader 2 (administered consecutively for 3 days) potently inhibits the proliferation of various human cancer cell lines, including Bortezomib (HY-10227)-resistant KM3/BTZ cells, with an IC₅₀ of 0.49 μM; meanwhile, this compound exhibits extremely low toxicity to normal human cells and has a high therapeutic window^[1].
PROTAC 20S proteasome subunit β5 degrader 2 (0.05-5 μM; 0-24 h) induces dose-dependent and time-dependent degradation of the 20S proteasome β5 subunit in FaDu cells, with a DC₅₀ of 0.16 μM; meanwhile, this compound also induces the aforementioned degradation in Bortezomib-resistant KM3/BTZ cells, accompanied by the accumulation of ubiquitinated proteins^[1].
PROTAC 20S proteasome subunit β5 degrader 2 (0.1-1 μM; 24 h) inhibits the migration of human pharyngeal squamous cell carcinoma FaDu cells in a dose-dependent manner in wound healing assays^[1].
PROTAC 20S proteasome subunit β5 degrader 2 (0.01-0.5 μM; 10 days) inhibits colony formation of FaDu pharyngeal squamous cell carcinoma cells in a dose-dependent manner^[1].
PROTAC 20S proteasome subunit β5 degrader 2 (0.01-10 μM; 24 h) induces apoptosis in a dose-dependent manner in human pharyngeal squamous cell carcinoma FaDu cells and bortezomib-resistant multiple myeloma KM3/BTZ cells, and alters cell cycle progression in a dose-dependent manner^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.