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].
In Vivo, 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].
In Vitro, 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].
References:
[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.
In Vivo, 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].
In Vitro, 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].
References:
[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.