Motugivatrep (SJP-0132), a transient receptor potential cation channel subfamily V member 1 (TRPV1) antagonist, is being developed as an ophthalmic drug for dry eye disease. Since the role of TRPV1 antagonists in skin carcinogenesis remains controversial, this study aimed to investigate whether motugivatrep promotes skin tumorigenesis using an ultra-short-term two-stage skin carcinogenesis model with Tg-rasH2 mice. Following initiation with a single dermal application of 7,12-dimethylbenz[a]anthracene, motugivatrep was applied topically at doses of 0, 150, 300, or 750 µg/50 µL/animal once a day to mouse skin for 7 weeks. The positive control group received 12-O-tetradecanoylphorbol-13-acetate (TPA) once weekly. No skin tumors or preneoplastic lesions were observed in any animals treated with motugivatrep. In contrast, treatment with TPA significantly increased skin tumor formation, confirming the validity of the assay. These results indicated that motugivatrep lacked skin tumor promotion activity in this Tg-rasH2 mice model, providing safety information regarding dermal exposure to motugivatrep.
