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The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells.
Krepler C, Chunduru SK, Halloran MB, He X, Xiao M, Vultur A, Villanueva J, Mitsuuchi Y, Neiman EM, Benetatos C, Nathanson KL, Amaravadi RK, Pehamberger H, McKinlay M, Herlyn M. Krepler C, et al. Among authors: mckinlay m. Clin Cancer Res. 2013 Apr 1;19(7):1784-94. doi: 10.1158/1078-0432.CCR-12-2518. Epub 2013 Feb 12. Clin Cancer Res. 2013. PMID: 23403634 Free PMC article.
Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-κB activation, and is active in patient-derived xenograft models.
Benetatos CA, Mitsuuchi Y, Burns JM, Neiman EM, Condon SM, Yu G, Seipel ME, Kapoor GS, Laporte MG, Rippin SR, Deng Y, Hendi MS, Tirunahari PK, Lee YH, Haimowitz T, Alexander MD, Graham MA, Weng D, Shi Y, McKinlay MA, Chunduru SK. Benetatos CA, et al. Among authors: mckinlay ma. Mol Cancer Ther. 2014 Apr;13(4):867-79. doi: 10.1158/1535-7163.MCT-13-0798. Epub 2014 Feb 21. Mol Cancer Ther. 2014. PMID: 24563541
Birinapant, a smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies.
Condon SM, Mitsuuchi Y, Deng Y, LaPorte MG, Rippin SR, Haimowitz T, Alexander MD, Kumar PT, Hendi MS, Lee YH, Benetatos CA, Yu G, Kapoor GS, Neiman E, Seipel ME, Burns JM, Graham MA, McKinlay MA, Li X, Wang J, Shi Y, Feltham R, Bettjeman B, Cumming MH, Vince JE, Khan N, Silke J, Day CL, Chunduru SK. Condon SM, et al. Among authors: mckinlay ma. J Med Chem. 2014 May 8;57(9):3666-77. doi: 10.1021/jm500176w. Epub 2014 Apr 15. J Med Chem. 2014. PMID: 24684347
IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis.
Vince JE, Wong WW, Khan N, Feltham R, Chau D, Ahmed AU, Benetatos CA, Chunduru SK, Condon SM, McKinlay M, Brink R, Leverkus M, Tergaonkar V, Schneider P, Callus BA, Koentgen F, Vaux DL, Silke J. Vince JE, et al. Among authors: mckinlay m. Cell. 2007 Nov 16;131(4):682-93. doi: 10.1016/j.cell.2007.10.037. Cell. 2007. PMID: 18022363 Free article.
Bivalent IAP antagonists, but not monovalent IAP antagonists, inhibit TNF-mediated NF-κB signaling by degrading TRAF2-associated cIAP1 in cancer cells.
Mitsuuchi Y, Benetatos CA, Deng Y, Haimowitz T, Beck SC, Arnone MR, Kapoor GS, Seipel ME, Chunduru SK, McKinlay MA, Begley CG, Condon SM. Mitsuuchi Y, et al. Among authors: mckinlay ma. Cell Death Discov. 2017 Jan 16;3:16046. doi: 10.1038/cddiscovery.2016.46. eCollection 2017. Cell Death Discov. 2017. PMID: 28149532 Free PMC article.
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