Toxicity of ACP-105: a substance used as doping in sports: application of in silico methods for prediction of selected toxicological endpoints

Abstract

ACP-105 is a novel non-steroidal Selective Androgen Receptor Modulator (SARM) used by athletes. Its action aims to increase muscle mass and is one of the options in testosterone replacement therapy. Its safety profile remains insufficiently explored, particularly regarding its toxicity in humans. The lack of information about the studied compound in the World Anti-Doping Agency (WADA) became the purpose of this study. Given the increasing use of such compounds in sports, a deeper understanding of their biological risks is crucial. This study not only fills the gap in available information but also contributes to the growing body of research on SARMs, providing insights into their potential hazards and guiding future investigations into their safety. This work aimed to use various in silico techniques to predict the toxicity of ACP-105, including acute toxicity, effects on internal organs, genotoxicity based on the Ames test, eye and skin irritation, and cardiotoxicity by testing hERG inhibitors. A preliminary safety analysis of the compound was based on its chemical structure and interactions with biological targets using various in silico techniques: qualitative (STopTox, ADMETlab, admetSAR, ProTox 3.0, and Toxtree 3.1.0) and quantitative (TEST 5.1.2, Percepta, VEGA QSAR 1.2.3, and SL-Tox) to ensure that the prediction results are as accurate as possible.