SynCraft: an integrated web server for ADMET-aware retrosynthesis and molecular design

The efficient design of drug candidates requires simultaneous consideration of synthetic feasibility and pharmacokinetic safety. However, current computational tools typically address retrosynthetic planning and ADMET evaluation as separate tasks, requiring users to manually transfer data between platforms and evaluate candidate molecules in a sequential and time-consuming manner. Here, we present SynCraft, a web server that integrates template-based retrosynthesis with real-time ADMET evaluation within a unified workflow. SynCraft accepts molecular input via SMILES, interactive drawing, or file upload, and performs automated multi-step retrosynthetic planning while simultaneously assessing the safety and drug-likeness of all intermediate compounds. ADMET properties are predicted using a multi-view learning framework, and potentially hazardous intermediates are automatically highlighted with intuitive, colour-coded warnings during route exploration. The server further provides integrated analysis tools, including synthetic accessibility and complexity scoring, drug-likeness evaluation, and interactive 2D/3D visualization, enabling users to seamlessly transition from route generation to detailed molecular assessment. Results are presented through an interactive interface that allows comparison of alternative synthetic routes, with downloadable outputs in standard formats. In a case study of imatinib, SynCraft automatically identifies genotoxic intermediates that are typically overlooked in conventional retrosynthesis workflows, demonstrating its practical utility for safety-aware route design. The web server is freely accessible at https://syncraft.denglab.org.