2026 年 13 巻 3 号 p. 103-117
Motugivatrep (SJP-0132) is a transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist and a potential therapeutic agent for dry eye disease. However, the possible carcinogenicity of TRPV1 antagonists has raised concerns. Therefore, this study aimed to evaluate the genotoxic and carcinogenic potential of motugivatrep by conducting standard genotoxicity assays and assessing carcinogenicity in Tg-rasH2 mice and rats following oral administration for 26 and 104 weeks, respectively. In the bacterial reverse mutation assay, no increase in the number of revertant colonies was observed at any concentration with or without metabolic activation. In the mouse lymphoma thymidine kinase assay, no increase in mutant fractions was observed under any treatment conditions, with or without metabolic activation. Oral administration of motugivatrep did not increase the number of micronucleated immature erythrocytes at doses up to 2000 mg/kg in the in vivo micronucleus assay in rats. In carcinogenicity studies in Tg-rasH2 mice and rats, no increase in tumor incidence in any organs/tissues of either sex was observed in the motugivatrep-treated groups at doses of up to 100 and 50 mg/kg/day, respectively, which correspond to systemic exposures exceeding the anticipated clinical levels. Overall, motugivatrep was negative for genotoxicity, and oral administration did not exhibit carcinogenic potential in rodents. These results suggest that ocular instillation of the motugivatrep ophthalmic formulation is unlikely to pose a carcinogenic risk to systemic organs and tissues.
