Background: Smac mimetics (also known as IAP antagonist) are a new class of
targeted drugs having a goal to suppress the IAPs, reestablishing the apoptotic pathways and
inducing cancer cell death. Therefore, development of Smac mimetics was considered an attractive
strategy for the development of new anticancer drugs. Lots of reviews have come in
yesteryears which mainly discussed the biology of IAPs and their role in cancer development.
None of these reviews focused on the chemical synthesis of Smac mimetics.
Methods: Literature study was done by using standard bibliographic search engines like
scifinder, pubmed etc. The characteristic features of screened articles were described in the
Results: The review gives an introduction of IAP proteins and Smac mimetics. Readers will
gain an overview of the development of Smac mimetics with representative examples of both
monovalent and bivalent Smac mimetics as anticancer agents and an understanding of their
structure-activity relationships. Chemical synthesis of biologically important Smac mimetics
was discussed briefly in this review.
Conclusion: Small molecules that mimic Smac are continuously progressing towards clinical
development. Smac mimetics are generally well tolerated and have demonstrated rapid suppression
of their target (the IAPs), activation of apoptosis and anti-tumor activity. Continuous
research has been done to generate even more insight into the function of IAP proteins to significantly
enhance the therapeutical potential of Smac mimetics.