Title:Recent Advances on Small-Molecule Survivin Inhibitors
Volume: 22
Issue: 9
Author(s): Min Xiao and Wei Li
Affiliation:
Keywords:
BIRC5 inhibitor, inhibitor of apoptosis proteins, protein-protein interaction inhibitor, small-molecule anticancer
agent, survivin and cancer, survivin inhibitor.
Abstract: Survivin, a member of the inhibitor of apoptosis proteins family, is highly expressed in most human
neoplasms, but its expression is very low or undetectable in terminally differentiated normal tissues.
Survivin has been shown to inhibit cancer cell apoptosis and promote cell proliferation. The overexpression
of survivin closely correlates with tumor progression and drug resistance. Because of its key role in tumor
formation and maintenance, survivin is considered as an ideal target for anticancer treatment. However, the
development of small-molecule survivin inhibitors has been challenging due to the requirement to disrupt
the protein-protein interactions. Currently only a limited number of survivin inhibitors have been developed in recent
years, and most of these inhibitors reduce survivin levels by interacting with other biomolecules instead of directly interacting
with survivin protein. Despite these challenges, developing potent and selective small-molecule survivin inhibitors
will be important both in basic science to better understand survivin biology and in translational research to develop potentially
more effective, broad-spectrum anticancer agents. In this review, the functions of survivin and its role in cancer
are summarized. Recent developments, challenges, and future direction of small-molecule survivin inhibitors are also discussed
in detail.