NSC 146109 hydrochloride is a selective activator of p53 with IC50 value ranges from 2.5 to >5 μg/mL [1].
Tumor protein p53 (p53) is a crucial protein in multicellular organisms and plays a pivotal role in preventing cancer formation. [1].
NSC 146109 hydrochloride is a potent p53 activator and has a higher activity than reported p53 activator RITA. When tested with breast tumor cell line MCF-7 cells, NSC 146109 hydrochloride treatment induced cell apoptosis and decreased cell viability through activating p53 expression which in turn up-regulated the expression of p21 [2]. In 16 tumor cells, NSC 146109 hydrochloride showed no clear genetic basis for the tumorigenic cell selectivity while had different affinity to different cell lines [1]. When tested with head and neck cancer (HNC) cell lines (high-expression of MDM4 while low-expression of p53, NSC 146109 hydrochloride treatment significantly suppressed cell growth and promoted cell apoptosis in a dose-dependent manner [3].
In mice model with head and neck cancer (HNC) cells subcutaneous xenograft, administration of NSC 146109 hydrochloride markedly inhibited cell growth and decreased tumor volume alone or combined with chemotherapy drug cisplatin which was regarded as a promising strategy for treating HNC in clinic [3].
References:
[1]. Dolma, S., et al., Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell, 2003. 3(3): p. 285-96.
[2]. Wang, H. and C. Yan, A small-molecule p53 activator induces apoptosis through inhibiting MDMX expression in breast cancer cells. Neoplasia, 2011. 13(7): p. 611-9.
[3]. Roh, J.L., J.Y. Park, and E.H. Kim, XI-011 enhances cisplatin-induced apoptosis by functional restoration of p53 in head and neck cancer. Apoptosis, 2014. 19(11): p. 1594-602.