Ex-Rad

Ex-Rad is an experimental drug being developed by Onconova Therapeutics and the U.S. Department of Defense. It is being studied as a radiation protection agent. Chemically, it is the sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone.

Clinical trials

The results of two Phase I clinical studies in healthy human volunteers indicate that subcutaneously injected Ex-Rad is safe and well tolerated, with "no evidence of systemic side effects". A study in mice demonstrated the efficacy of Ex-Rad by increasing the survival rate of mice exposed to typically lethal whole-body irradiation. The study tested oral and parenteral administration of Ex-Rad for both pre- and post-exposure radiomitigation.
Research on Ex-Rad has involved collaboration with the Armed Forces Radiobiology Research Institute, the Department of Biochemistry and Molecular & Cellular Biology at Georgetown University, Long Island University's Arnold & Marie Schwartz College of Pharmacy, and the Department of Oncological Sciences at the Mt. Sinai School of Medicine.

Mechanism of action

Onconova reports that Ex-Rad protects cells exposed to radiation against DNA damage, and that the drug's mechanism of action does not involve scavenging free radicals or arresting the cell cycle. Instead, they claim it employs a "novel mechanism" involving "intracellular signaling, damage sensing, and DNA repair pathways". Ex-RAD is a chlorobenzylsulfone derivative that works after free radicals have damaged DNA. Onconova CEO Ramesh Kumar believes this is a better approach than trying to scavenge free radicals. “Free radicals are very short-lived, and so the window of opportunity to give a drug is very narrow,” he says. In cell and animal models, Ex-RAD protects hematopoietic and gastrointestinal tissues from radiation injury when given either before or after exposure.