LQZ-7I is asurvivin inhibitor through inhibition of survivin dimerization. It effectively inhibited xenograft tumor growth and inducedsurvivin loss in tumor when given orally.
Survivin, a homodimeric member of the inhibitor of apoptosis protein (IAP) family, is required for cancer cell survival and overexpressed in almost all solid tumors. LQZ-7I is a survivin inhibitor. It has improved cytotoxicity with an IC50 of 3.1 µM against C4-2 cells and 4.8 µM against PC-3 cells. LQZ-7I significantly decreased the SEAP (secreted alkaline phosphatase) reporter expression. Furthermore, it significantly inhibited survivin dimerization. In C4-2 and PC-3 cells, LQZ-7I treatment reduced the expression of survivin in a time-dependent manner. Specifically, LQZ-7I treatment reduced the half-life of survivin from 2.2 and 2.3 hrs to 50 and 25 minutes in C4-2 and PC-3 cells, respectively. Moreover, LQZ-7I induced cleavage of caspase 3 in a dose dependent manner in both cell lines. 3 µM LQZ-7I induced ~48% and ~39% apoptosis in C4-2 and PC-3 cells, respectively. In vivo, LQZ-7I treatment at 100 mg/kg significantly suppressed tumor growth without any notable adverse effect on the mice as indicated by lacking changes in body weight[1].
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