Description
Mouse double minute 2 protein (MDM2) is an E3 ubiquitin-protein ligase that binds and ubiquitinates the tumor suppressor p53, leading to its degradation by the proteasome. SP 141 is a cell-permeable inhibitor of MDM2 (Ki = 28 nM). Binding of MDM2 by SP 141 promotes its auto-ubiquitination and proteasomal degradation. SP 141 induces cell cycle arrest and apoptosis in breast and pancreatic cancer cell lines and inhibits xenograft tumor growth in vivo. This compound has a short half-life in plasma and wide tissue distribution in tumor-bearing nude mice.
References
[1]. vassilev lt, vu bt, graves b, et al. in vivo activation of the p53 pathway by small-molecule antagonists of mdm2. science. 2004 feb 6;303(5659):844-8.
[2]. wang w, qin jj, voruganti s, et al. the pyrido[b]indole mdm2 inhibitor sp-141 exerts potent therapeutic effects in breast cancer models. nat commun. 2014 oct 1;5:5086.
[3]. wang w, qin jj, voruganti s, et al. identification of a new class of mdm2 inhibitor that inhibits growth of orthotopic pancreatic tumors in mice. gastroenterology. 2014 oct;147(4):893-902.e2.
[4]. nag s, qin jj, voruganti s, et al. development and validation of a rapid hplc method for quantitation of sp-141, a novel pyrido[b]indole anticancer agent, and an initial pharmacokinetic study in mice. biomed chromatogr. 2015 may;29(5):654-63.
