The Inhibitors of apoptosis (IAP) are a family of functionally and structurally related proteins. The human family has eight members: NAIP (BIRC1), BIRC2 (cIAPl), BIRC3 (cIAP2), XIAP (BIRC4), BIRC5 (survivin), BIRC6 (apollon), BIRC7 (livin) and BIRC8. All members of the family contain 1-3 copies of a 70-80 amino acid motif known as BIR (baculovirus IAP repeat). The IAPs have garnered interest as drug targets with antineoplastic [1,9] and immunomodulatory [3] potential. Small molecule, antagonistic, peptide mimetics have been described [5-6,8].

1. Bai L, Smith DC, Wang S. (2014) Small-molecule SMAC mimetics as new cancer therapeutics. Pharmacol. Ther., 144 (1): 82-95. [PMID:24841289]

2. Donnell AF, Michoud C, Rupert KC, Han X, Aguilar D, Frank KB, Fretland AJ, Gao L, Goggin B, Hogg JH et al.. (2013) Benzazepinones and benzoxazepinones as antagonists of inhibitor of apoptosis proteins (IAPs) selective for the second baculovirus IAP repeat (BIR2) domain. J. Med. Chem., 56 (20): 7772-87. [PMID:24083782]

3. Estornes Y, Bertrand MJ. (2014) IAPs, regulators of innate immunity and inflammation. Semin. Cell Dev. Biol.,  [Epub ahead of print]. [PMID:24718315]

4. Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, Eckhardt SG et al.. (2012) Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J. Med. Chem., 55 (9): 4101-13. [PMID:22413863]

5. Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. (2014) Apoptosis and molecular targeting therapy in cancer. Biomed Res Int, 2014: 150845. [PMID:25013758]

6. Hennessy EJ, Adam A, Aquila BM, Castriotta LM, Cook D, Hattersley M, Hird AW, Huntington C, Kamhi VM, Laing NM et al.. (2013) Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J. Med. Chem., 56 (24): 9897-919. [PMID:24320998]

7. Ho SS, Go ML. (2013) Restraining the flexibility of the central linker in terameprocol results in constrained analogs with improved growth inhibitory activity. Bioorg. Med. Chem. Lett., 23 (22): 6127-33. [PMID:24080463]

8. Peng Y, Sun H, Nikolovska-Coleska Z, Qiu S, Yang CY, Lu J, Cai Q, Yi H, Kang S, Yang D et al.. (2008) Potent, orally bioavailable diazabicyclic small-molecule mimetics of second mitochondria-derived activator of caspases. J. Med. Chem., 51 (24): 8158-62. [PMID:19049347]

9. Saleem M, Qadir MI, Perveen N, Ahmad B, Saleem U, Irshad T, Ahmad B. (2013) Inhibitors of apoptotic proteins: new targets for anticancer therapy. Chem Biol Drug Des, 82 (3): 243-51. [PMID:23790005]

10. Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ et al.. (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell, 131 (4): 669-81. [PMID:18022362]