Drug intelligence / Profile preview

Antp-DNMAML

Development stage
Discontinued
Lead developer
Imperial College London
Modality
Recombinant Proteins and Enzymes, Peptides
Administration
Intramuscular, Intraperitoneal, Intravenous, Subcutaneous
01

Overview

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.

Other names
ANTP/DN MAMLANTP/DN-MAMLAntp-DNMAML fusion proteinrecombinant ANTP-dnMAMLrecombinant ANTP/DN-MAML
02

Targets

NOTCH2 (Neurogenic locus notch homolog protein 2)NOTCH (Neurogenic locus notch homolog protein 3)NICD1 (Notch1 intracellular domain)MAML1 (Mastermind-like protein 1)NICD-RBPJ (Notch intracellular domain-Recombination signal binding protein for immunoglobulin kappa J region complex)

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