Ex-Rad (or Ex-RAD; recilisib sodium (
INN,
USAN); development code ON 01210.Na) is an experimental drug being
developed by Onconova Therapeutics and the
U.S. Department of Defense.[1] It is being studied as a radiation protection agent.[2] Chemically, it is the sodium salt of 4-carboxystyryl-4-chlorobenzylsulfone.[3]
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".[4] 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.[1]
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".[4] 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.[5]
^Ghosh, Sanchita P.; Perkins, Michael W.; Hieber, Kevin; Kulkarni, Shilpa; Kao, Tzu-Cheg; Reddy, E. Premkumar; Reddy, M. V. Ramana; Maniar, Manoj; Seed, Thomas; Kumar, K. Sree (2009). "Radiation Protection by a New Chemical Entity, Ex-Rad: Efficacy and Mechanisms". Radiation Research. 171 (2): 173–9.
Bibcode:
2009RadR..171..173G.
doi:
10.1667/RR1367.1.
PMID19267542.
S2CID207252424.
^Reliene, Ramune; Pollard, Julianne M.; Sobol, Zhanna; Trouiller, Benedicte; Gatti, Richard A.; Schiestl, Robert H. (2009). "N-acetyl cysteine protects against ionizing radiation-induced DNA damage but not against cell killing in yeast and mammals". Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 665 (1–2): 37–43.
doi:
10.1016/j.mrfmmm.2009.02.016.
PMID19427509.
^Mansour, Heba H.; Hafez, Hafez F.; Fahmy, Nadia M.; Hanafi, Nemat (2008). "Protective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats". Biochemical Pharmacology. 75 (3): 773–80.
doi:
10.1016/j.bcp.2007.09.018.
PMID18028880.
^Demirel, C; Kilciksiz, S; Evirgen-Ayhan, S; Gurgul, S; Erdal, N (2010). "The preventive effect of N-acetylcysteine on radiation-induced dermatitis in a rat model". Journal of the Balkan Union of Oncology. 15 (3): 577–82.
PMID20941831.