PharmAgents2: Towards Autonomous End-to-End Drug Discovery
Haichuan Tan, Bowen Gao, Tao Huang, Jiaxin Tan, Xin Hong, Baoguo Yao, Yifei Wang, Zhichao Deng 等 25 位作者
原文摘要
Drug discovery requires continuous scientific decision-making across a vast research space. We introduce PharmAgents2, an autonomous system for end-to-end drug discovery that combines knowledge-enhanced decision-making with organized large-scale exploration. Paper2Skill extracts transferable scientific decision knowledge from public sources and, together with expert-developed skills, supports research decisions. Self-Scaling Discovery expands exploration through parallel agents inheriting research context and decision-making capabilities across targets, scientific hypotheses, and discovery strategies. We introduce PharmAgents-Bench v0.1, comprising 121 questions across nine decision scenarios and three end-to-end tasks assessed with expert-defined process rubrics. PharmAgents2 outperforms evaluated baselines in most decision categories and achieves the highest process scores on all three end-to-end tasks. In three real-world studies, autonomous investigations generated findings subsequently supported by human-executed experiments. For LpxH, PharmAgents2 hypothesized a previously unreported allosteric site and screened compounds against it, identifying a novel inhibitor scaffold with experimentally confirmed inhibitory activity and binding. For JAK1, it prioritized a covalent inhibition strategy and nominated compounds with experimentally demonstrated activity. Starting from a known bioactive molecule, Self-Scaling Discovery explored candidate targets across the proteome and identified a new binding target, with the interaction subsequently confirmed experimentally. PharmAgents2 represents a prototype of a virtual pharmaceutical company, marking a step toward autonomous end-to-end drug discovery.
cs.AI · q-bio.QM