The insulin-like growth factor-1 receptor (IGF1R) is involved in cell survival and metabolic signaling and has an important connection with pancreatic β-cell function. In this study, 15 bioactive compounds were screened against the human IGF1R kinase domain using molecular docking together with SwissADME and ProTox-3.0 analysis. CB-Dock2 identified five binding cavities, with P1 emerging as the preferred region for most of the compounds. The docking setup was further supported by redocking of the crystallographic BMI ligand, which reproduced a near-native pose with a minimum heavy-atom RMSD of 0.69 Å.
Among the screened compounds, Puerarin showed the strongest docking score (−10.1 kcal/mol). Mangiferin and Silibinin followed with scores of −9.1 kcal/mol, while Wedelolactone, Baicalein, and Paeoniflorin also showed favorable binding scores. The ADMET results, however, showed that strong docking did not always correspond to favorable drug-like properties. Puerarin and Paeoniflorin showed no high-confidence ProTox toxicity alerts, although both had limitations related to predicted oral absorption. Several other compounds showed potential concerns involving CYP interactions or predicted respiratory, cardiac, or immunological toxicity. Mangiferin produced an unusually low predicted oral LD₅₀ of 2 mg/kg, which was treated cautiously as a model-derived result.
Overall, the study identified several compounds with promising structural compatibility toward IGF1R. Puerarin was particularly notable because it combined the strongest docking result with a comparatively limited predicted toxicity profile, although its low predicted gastrointestinal absorption remains a limitation. These findings provide a useful basis for further experimental studies to confirm IGF1R binding and explore the possible effects of these compounds on pancreatic β-cell function.