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Antp-DNMAML (also known as TR4) is a recombinant hybrid fusion protein consisting of a truncated version of the Mastermind-like (MAML) protein, which acts in a dominant-negative (DN) fashion to inhibit Notch signaling, fused to the cell-penetrating peptide Antennapedia (Antp). Developed by Trojantec in collaboration with Imperial College London, the therapeutic is designed to translocate across cell membranes and into the nucleus. Once inside, the dominant-negative MAML peptide competitively binds to the Notch intracellular domain (NICD) and the CSL (RBPJ) transcription factor, preventing the recruitment of endogenous co-activators and thereby blocking the assembly of the active Notch transcription complex. This inhibition suppresses downstream Notch target genes, leading to the reversion of transformed phenotypes, inhibition of anchorage-dependent growth, and induction of apoptosis in cancer cells. Antp-DNMAML demonstrated preclinical efficacy in breast and colon cancer models, but its development was discontinued when Trojantec ceased operations.
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