Suramin

Suramin is a reversible, competitive inhibitor of protein-tyrosine phosphatases (PTPases) [1], demonstrating potent inhibition against sirtuins: SirT1 (IC50=297 nM), SirT2 (IC50=1.15 μM), and SirT5 (IC50=22 μM) [2]. It also acts as a competitive inhibitor of reverse transcriptase (DNA topoisomerase II: IC50=5 μM) [3] [4] and exhibits potent inhibition of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) [5]. Additionally, Suramin effectively inhibits IP5K, showcasing its antiparasitic, anti-neoplastic, and anti-angiogenic properties [6] [7] [8].

Suramin Sodium Salt (BAY-205) is a sodium salt form of suramin, a polysulphonated naphthylurea with potential antineoplastic activity. Suramin blocks the binding of various growth factors, including insulin-like growth factor I (IGF-I), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and tumor growth factor-beta (TGF-beta), to their receptors, thereby inhibiting endothelial cell proliferation and migration. This agent also inhibits vascular endothelial growth factor (VEGF)- and basic fibroblast growth factor (bFGF)-induced angiogenesis; retroviral reverse transcriptase; uncoupling of G-proteins from receptors; topoisomerases; cellular folate transport; and steroidogenesis.

NF864, a suramin analog, is a P2X1 receptor inhibitor.

NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that shows strong antitumor activity. It inhibited topoisomerase II activity and stabilized topoisomerase II-DNA cleavable complexes. The DNA breaks occurred within 1h after treatment with NK314 even without digestion of topoisomerase II by proteinase K, whereas etoposide required digestion of the enzyme protein in cleavable complex to detect DNA breaks. Pretreatment with topoisomerase II catalytic inhibitors, ICRF-193 and suramin, reduced both cleavable complex-mediated DNA breaks and proteinase K-independent DNA breaks, but protease inhibitors and nuclease inhibitors only decreased the latter.