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April 1, 2014
07:10 EDTTLOGTetraLogic announces publication of preclinical characterization of birinapant
TetraLogic Pharmaceuticals announced that data published in the April issue of Molecular Cancer Therapeutics further advances the preclinical characterization of its lead SMAC-Mimetic birinapant, which is currently being tested in Phase 1 and Phase 2 clinical trials for hematological malignancies and solid tumors. The experiments described in the publication demonstrate that birinapant bound to the BIR3 domains of cIAP1, cIAP2, XIAP, and the BIR domain of ML-IAP in vitro and induced the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2, resulting in induction of tumor cell death. Birinapant preferentially targeted the TRAF2-associated cIAP1 and cIAP2 with subsequent inhibition of TNF-induced NF-{kappa}B activation. The activity of a variety of chemotherapeutic cancer drugs was potentiated by birinapant, and tumor growth in multiple primary patient–derived xenotransplant models was inhibited by birinapant at well-tolerated doses.
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