TMPyP4 tosylate (TMP 1363) is a quadruplex-specific ligand, which inhibits the interaction between G-quadruplexes and IGF-1[1]. TMPyP4 tosylate (TMP 1363) is atelomerase inhibitor with antitumor effects in osteosarcoma cell lines[2].
The biological functions of G-quadruplexes are closely related to the binding of some proteins. Insulin-like growth factor type I (IGF-1), as a significant modulator of cell growth and development, may serve as a quadruplex-binding protein.TMPyP4 tosylate (TMP 1363) is a quadruplex-specific ligand, which inhibits the interaction between G-quadruplexes and IGF-1. IGF-1 shows a binding specificity for G-quadruplex structures, especially the G-quadruplex structure with a parallel topology. The quadruplex-specific ligands TMPyP4 and PDS (Pyridostatin) can inhibit the interaction between G-quadruplexes and proteins[1].
TMPyP4 is a cationic porphyrin that intercalates into and stabilizes G-quadruplexes, which are formed by DNA and RNA sequences composed of blocks of guanine residues[2]. TMPyP4 induces telomere shortening, and inhibition of the cell growth in HOS and Saos-2 with over 17% apoptosis rates.[3]. TMPyP4 inhibits telomerase activity (IC50 ≤ 50 µM), blocking the clonogenic growth and migration of cancer cells in culture and in vivo[4]. TMPyP4 potently suppressed cell viability and induced the apoptosis of SW480 cells in a dose-dependent manner. In addition, the downregulation of Wnt, β-catenin and cyclinD1 expression levels was detected in TMPyP4-treated SW480 cells.[5].
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