Evasion of apoptosis is an important reason for tumor cells to resist the anticancer drugs in cancer therapy. As a
critical regulator, the inhibitor of apoptosis proteins (IAPs) can block the apoptosis by inhibiting the activities of caspases.
Scientists find that IAPs are over-expressed in many cancer cells, such as leukemia and B-cell lymphoma, which elucidate
that high levels of IAPs are closely related to tumorigenesis and cancer development. Thus, targeting IAPs may be an attractive
strategy for anti-tumor treatment. As an endogenous antagonist of IAPs, second mitochondria-derived activator of
caspases (Smac) can suppress their activities through directly binding to IAPs. Based on structural biology study, Smac
interacts with IAPs through the Ala-Val-Pro-Ile (AVPI) tetra-peptide of Smac. Therefore, many agents have been studied
to suppress the IAPs which result in the activation of caspases and subsequently induce the apoptosis of tumor cells based
on mimicking AVPI peptide strategy. In this review, the functions of IAPs in apoptosis and the recent advance of IAPs antagonists
will be discussed.