1000313-40-5

UK-101 is a potent and selective immunoproteasome β1i (LMP2) inhibitor with an IC50 value of 104 nM, displays 144- and 10-fold selectivity over β1c (IC50=15 μM) and β5 subunit (IC50=1 μM), respectivey[1]. UK-101 induces cell apoptosis and can be used for the study of prostate cancer[2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Proteasome

IC50: 104 nM (LMP2) IC50: 15 μM (immunoproteasome β1c) IC50: 1 μM (immunoproteasome β5)[1]

UK-101 (2-8 μM; 24 hours) induces cell cycle arrest and increases the number of the PC-3 cells arrest in G1 phase of the cell cycle[2]. UK-101 (2-8 μM; 24 hours) induces cell apoptosis, shows a minimal increase in late apoptosis, but has no significant increase in early apoptosis[2]. UK-101 (1-8 μM; 24 hours) induces cells accumulation in the G1 phase of the cell cycle, it increases p27 accumulation and significantly increases PARP cleavage as a dose-dependent manner[2]. Cell Cycle Analysis[1] Cell Line: PC-3 cells Concentration: 2 μM; 8 μM Incubation Time: 24 hours Result: Induced G1 cell cycle arrest in PC-3 cells. Apoptosis Analysis[1] Cell Line: PC-3 cells Concentration: 2 μM; 8 μM Incubation Time: 24 hours Result: Increased cell apoptosis as a dose-dependent manner. Western Blot Analysis[1] Cell Line: PC-3 cells Concentration: 1 μM; 2 μM; 8 μM Incubation Time: 24 hours Result: Increased PARP cleavage and p27 accumulation as a dose-dependent manner.

UK-101 (intraperitoneal injection; 1-3 mg/kg; twice a week; 3 weeks) decreases tumor volume as a dose-dependent manner, it significantly decreases tumor volume at a dose of 3 mg/kg. Additionally, UK-101-treated mice is suffering less systemic toxicity and the weights of mice treated with UK-101 remains steady over the 3-week treatment period[2]. Animal Model: Subcutaneously implanted PC-3 cells in 6-week-old male BALB/c athymic nude mice[2] Dosage: 1 mg/kg; 3 mg/kg Administration: Intraperitoneal injection; twice a week; 3 weeks Result: Inhibited tumour growth in the prostate cancer mouse xenograft model.

[1]. de Bruin G, et al. Structure-based design of β1i or β5i specific inhibitors of human immunoproteasomes. J Med Chem. 2014 Jul 24;57(14):6197-209.

[2]. Wehenkel M, et al. A selective inhibitor of the immunoproteasome subunit LMP2 induces apoptosis in PC-3 cells and suppresses tumour growth in nude mice. Br J Cancer. 2012 Jun 26;107(1):53-62.