PKT16

PKT16 is a synthetic, N-methylated peptide derived from the thrombospondin-1 (TSP-1) protein, designed as a first-in-class therapeutic agent for cancer treatment. It acts as an agonist of CD47 and induces a unique, caspase-independent programmed necrotic cell death in malignant cells through calcium-dependent mechanisms. This mode of action is distinct from necroptosis or ferroptosis and involves intracellular Ca2+ deregulation leading to mitochondrial damage and cell cycle arrest. PKT16 specifically targets cancer cells—including those with poor prognosis or resistance markers—while sparing healthy tissues such as hematopoietic precursors. The peptide also triggers immunogenic cell death by exposing calreticulin on the plasma membrane and releasing ATP and HMGB1, thereby stimulating anticancer immune responses in vivo. Preclinical studies have demonstrated its efficacy against chronic lymphocytic leukemia (CLL) and various solid tumors, with improved cytotoxicity compared to earlier TSP-1 mimetics like PKHB1[2][3][6]. Developed using solid-phase peptide synthesis (SPPS), PKT16 exhibits high solubility in physiological saline and strong stability in plasma[3]. As of 2025, it remains at the preclinical development stage.