Background:

SP 141 is a specific, potent and selective small-molecule antagonist of MDM2 with Ki value of 28±6 nM [2][3][4].

Mouse double minute 2 protein (Mdm2) is an ubiquitin ligase that promotes p53 degradation, a tumor suppressor that controls a major pathway protecting cells from malignant transformation [1].

SP 141 is a potent and selective MDM2 inhibitor. In breast cancer cell lines, SP-141 reduced cell viability with IC50 less than 1 μM (0.39-0.91 μM) and inhibited cancer cell colony formation in a concentration-dependent way. SP-141 also increased apoptosis and concentration-dependently inhibited cell proliferation. In both MCF-7 and MDA-MB-468 cells, SP-141 increased the degradation rate of the MDM2 protein [2].

In nude mice bearing MCF-7 and MDA-MB-468 xenograft tumours, intraperitoneal (i.p.) injection of SP-141 inhibited tumour growth by