PROTAC-DB 4.0 发布，扩充至 15502 条 PROTAC 并加入大模型自然语言查询
PROTAC-DB 4.0: an expanded knowledgebase of targeted protein degradation modalities with AI-powered knowledge discovery
PROTAC-DB 4.0 发布，收录 15502 条 PROTAC、24798 条分子胶（MG）和 272 条 XTAC 条目，并新增基于大语言模型与检索增强生成的自然语言查询系统。相比上一版本，该版本覆盖 PROTAC、分子胶和 X 功能靶向嵌合体（XTAC）等主要靶向降解与诱导邻近技术，扩充了实验注释、来自专利的化合物以及按模态划分的数据字段。新增的查询系统把结构化数据库记录与科学文献连接起来，支持在 PROTAC、MG 和 XTAC 之间进行知识发现。
来源：Nucleic Acids Research · doi.org
Proteolysis-targeting chimeras (PROTACs) represent an emerging therapeutic modality that harnesses the ubiquitin-proteasome system to induce targeted protein degradation (TPD). Their event-driven and catalytic mechanisms provide new opportunities to target previously undruggable proteins. However, the rapid expansion of TPD technologies, including molecular glues (MGs) and X-functional targeting chimeras (XTACs), together with the increasing application of artificial intelligence (AI) in degrader design, highlights the need for comprehensive and continuously updated data resources. Here, we present PROTAC-DB 4.0, an expanded knowledgebase covering major targeted degradation and induced-proximity technologies. Compared with the previous version, PROTAC-DB 4.0 contains 15 502 PROTAC entries, together with 24 798 MG entries and 272 XTAC entries, with expanded experimental annotations, patent-derived compounds, and modality-specific data fields. A major advancement in PROTAC-DB 4.0 is the integration of a large language model and retrieval-augmented generation-based natural language query system, which connects structured database records with scientific literature to enable intuitive knowledge discovery across PROTACs, MGs, and XTACs. By combining comprehensive data curation with AI-assisted information retrieval, PROTAC-DB 4.0 provides an accessible platform to support degrader discovery, data-driven modeling, and rational design of next-generation targeted degradation and induced-proximity therapeutics. PROTAC-DB 4.0 is freely accessible at http://cadd.zju.edu.cn/protacdb/.