First multifaceted ADME profile of ACP-105 (CAS: 1048998-11-3): a novel non-steroidal selective androgen receptor modulator used as doping in sports—integrative in silico toxicological studies for clinical and forensic toxicology purposes

ACP-105 (CAS: 1048998-11-3) is a novel non-steroidal selective androgen receptor modulator (SARM), increasingly detected in anti-doping analyses, yet lacking a comprehensive ADME profile. This study provides the first integrative in silico characterization of ACP-105's ADME properties using seven independent methods (ADMETlab 3.0, ADMET Predictor 12.0, ACD/Percepta, SwissADME, pkCSM, XenoSite and DruMAP). The compound demonstrated high gastrointestinal absorption (up to 100%), moderate lipophilicity (LogP 3.0-3.52), low solubility (LogS ~ - 4.1 to - 4.4), and Caco-2 permeability ranging from 13.6 to 152 × 10^-6 cm/s. It shows strong plasma protein binding (77-99%), minimal free plasma fraction (< 1%), and variable tissue distribution (Vd 0.18-12 L/kg). Blood-brain barrier penetration was predicted in most models. Metabolic profiling identified six metabolites (M1-M6), primarily formed via CYP3A4, with additional contributions from CYP2C9, CYP2C19, and CYP2D6. ACP-105 is a consistent substrate for CYP3A4 (82-100%) and likely undergoes stable and unstable oxygenation, N-dealkylation, and UGT conjugation. Interactions with DNA/protein and potential cyanide release were also predicted. Clearance predictions varied (7.175-3.86 × 10^-5 mL/min/kg), with a short half-life (~ 1.18 h), and no OCT2-mediated renal excretion expected. These findings provide a foundational ADME profile of ACP-105, essential for interpreting exposure in clinical toxicology and supporting evidence in forensic investigations involving illicit use.