Analysis of the proteomic profile in serum of irradiated nonhuman primates treated with Ex-Rad, a radiation medical countermeasure

There are currently four radiation medical countermeasures that have been
approved by the United States Food and Drug Administration to mitigate
hematopoietic acute radiation syndrome, all of which are repurposed
radiomitigators. The evaluation of additional candidate drugs that may
also be helpful for use during a radiological/nuclear emergency is
ongoing. A chlorobenzyl sulfone derivative (organosulfur compound) known
as Ex-Rad, or ON01210, is one such candidate medical countermeasure, being
a novel, small-molecule kinase inhibitor that has demonstrated efficacy in
the murine model. In this study, nonhuman primates exposed to ionizing
radiation were subsequently administered Ex-Rad as two treatment schedules
(Ex-Rad I administered 24 and 36 h post-irradiation, and Ex-Rad II
administered 48 and 60 h post-irradiation) and the proteomic profiles of
serum using a global molecular profiling approach were assessed. We
observed that administration of Ex-Rad post-irradiation is capable of
mitigating radiation-induced perturbations in protein abundance,
particularly in restoring protein homeostasis and immune response and
mitigating hematopoietic damage, at least in part after acute exposure.
Taken together, restoration of functionally significant pathway
perturbations may serve to protect damage to vital organs and provide
long-term survival benefits to the afflicted population.