Toxicity profile of the new compound XC221GI from pre-clinical studies

Abstract

The major feature of COVID-19 is intensive virus-induced inflammation in vital body organs and spatiotemporal dysregulation of pro- and anti-inflammatory cytokines and chemokines synthesis. All this leads to unpredicted clinical progression and high risk of "cytokine storm" development. The "cytokine storm" is the pathogenetic basis for further development of life-threatening complications. Thus, there is a huge need to select effective and safe approaches that allow to control virus-induced inflammation as a part of preventive anti-inflammatory therapy.
 This article presents toxicological characteristics of the original low-molecular compound XC221GI (1-[2-(1-methylimidazole-4-yl)-ethyl]perhydroazin-2,6-dione) from pre-clinical studies.
 The obtained results demonstrate that the XC221GI does not have any toxic effect in repeated long-term administration. The compound was well tolerated by all animals. The no-observed-adverse-effect level (NOAEL) was 30 mg/kg per day for dogs and 450 mg/kg per day for rats. There were no effects of XC221GI on blood count, hematopoiesis and hemostasis. As well as no cytotoxic, mutagenic, genotoxic, carcinogenic properties or anaphylactogenic and immunotoxic activity were revealed for XC221GI. All known data enable to classify XC221GI as a low toxic compound and consider its safety profile as reasonably favorable.

Curtailing virus-induced inflammation in respiratory infections: emerging strategies for therapeutic interventions

“…A study of reproductive toxicity performed in adult male and female rats, application of XC221GI in a daily dose of 17.4 or 174 mg/kg, an equivalent of one and ten therapeutic doses in humans, led to no changes in the fertility index or patterns or percentage of the post-implantation death. No fetal, prenatal or postnatal defects were observed (Suhanova et al, 2021). The study of immune responses did not reveal any adverse effects of XC221GI on the antibody formation, the number of T-and B-lymphocytes or phagocyte activity.…”

“…XC221GI exerted no influence on the blood cells, the hematopoiesis or the hemostasis. The dose of no apparent adverse effect (NOAEL) was 30 mg/kg per day for dogs and 450 mg/kg per day for rats (Suhanova et al, 2021).…”

“…No animal was observed throughout the periods of dosing and recovery. In vivo experiments showed no signs of toxicity or other undesirable effects after a single administration of XC221GI to outbred mice and rats of both sexes at a dose of 5,000 mg/kg, as well as after repeated administration to rats, rabbits, and dogs of both sexes in studies with 2 weeks, 4 weeks, 30-day and 3-month dosing of XC221GI at the doses of 6-174 mg/kg per day, which, after taking into account interspecies conversion factors, corresponds to the range of human therapeutic doses of one to ten, with proposed daily therapeutic dose in humans being 200 mg (Suhanova et al, 2021).…”