Dimesna

Dimesna is the disodium salt form of dithio-ethane sulfonate, a dimer of mesna and a disulfide bond disrupting agent (DDA), with uroprotective, nephroprotective, chemoprotective, chemosensitizing and chemo-enhancing activities. Upon administration, dimesna is able to modify cysteine on various proteins, such as the kinases EGFR, MET and ROS1, thereby disrupting extracellular disulfide bonds and modulating the activity of these proteins. This inhibits their signaling pathways and downregulates proliferative signaling in cancer cells in which these kinases are overexpressed. This may also enhance the activity of other kinase inhibitors targeting the same proteins. In the kidneys, dimesna undergoes reduction to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites acrolein and 4-hydroxy-ifosfamide, resulting in their detoxification. This agent also inhibits cyclophosphamide-induced hemorrhagic cystitis. In addition, dimesna reduces toxicities associated with taxanes and platinum-based chemotherapeutic agents.