In vitro mutagenic risk of ibutamoren

doi:10.19803/j.1672-8629.20260087

Abstract

Abstract: Objective To evaluate the in vitro mutagenic risk of ibutamoren using multiple genotoxicity assays. Methods The genotoxic potential of ibutamoren was estimated via computer modeling based on quantitative structure-activity relationships (Dereck and Sarah models) before being validated via bacterial reverse mutation assays, mice lymphoma gene mutation assay, and PIG-A gene mutation assay. Five bacterial strains were tested in the presence or absence of a metabolic activation system that contained ibutamoren. MLA assays were performed using L5178Y cells and ibutamoren under three treatment conditions (+S9/3 h, -S9/3 h, -S9/24 h). The relative proliferation rate (RPD) was calculated for TK6 cells exposed to ibutamoren at different concentrations for 4 hours (+S9) to assess cytotoxicity, and the incidence of mutant cells (CD55^-CD59^-/CD19⁺) was detected. Results Ibutamoren was mutagenic to TA98 cells in the absence of S9 and under metabolic activation by rat liver S9, but not to L5178Y cells under any of the three treatment conditions (+S9/3 h, -S9/3 h,-S9/24 h). Compared to the solvent control group, ibutamoren at 150 μg·mL^-1 significantly increased PIG-A gene mutation under metabolic activation by 2%S9 (P<0.001) in a dose-dependent manner. Conclusion Benzaldehyde, a metabolite of ibutamoren, can possibly be a contributor to its mutagenicity, but the precise mechanism needs to be investigated.

Key words: Ibutamoren, Ghrelin Receptor (GHSR1a) Agonist, Mutagenic Risk, Bacterial Reverse Mutation Assay, Mouse Lymphoma Assay (MLA), In vitro PIG-A Gene Mutation Assay, Structure-Activity Analysis, Mice

CLC Number:

R965.3

Ye Qian, Kou Xiaoxuan, Niu Qianyi, Song Jie, Li Xiaoyu, Wen Hairuo. In vitro mutagenic risk of ibutamoren[J]. Chinese Journal of Pharmacovigilance, 2026, 23(8): 841-847.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20260087

https://zgywjj.magtechjournal.com/EN/Y2026/V23/I8/841

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