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 [1-2,10] and immunomodulatory [4] potential. Small molecule, antagonistic, peptide mimetics have been described [2,6-7,9].

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7. 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]

8. 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]

9. 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]

10. 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]

11. 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]