MTI-101

**MTI-101** is a first-in-class cyclic peptidomimetic derived from the linear D-amino acid peptide HYD1, developed by Modulation Therapeutics for oncology indications. It binds to a **CD44/ITGA4** complex on cancer cell surfaces, triggering **necrotic cell death** through rapid intracellular **calcium overload** via activation of STIM1 and store-operated calcium channels including **TRPC1**, leading to reactive oxygen species production, mitochondrial membrane depolarization, ATP depletion, and independence from caspase activation or RIPK pathways. MTI-101 demonstrates enhanced potency against relapsed multiple myeloma cells and primary patient samples compared to newly diagnosed ones, shows synergy with bortezomib in vitro and in vivo (improving survival in 5TGM1 mouse models), and exhibits activity in prostate cancer, lung cancer models (synergizing with erlotinib/osimertinib/cisplatin), and reduced tumor invasion in vivo.[1][4][7][10][11]