Ge Jingxuan, Li Shimeng, Weng Gaoqi, Wang Huating, Fang Meijing, Sun Huiyong, Deng Yafeng, Hsieh Chang-Yu, Li Dan, Hou Tingjun
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 Zhejiang, China.
CarbonSilicon AI Technology Company, Ltd., Hangzhou 310018Zhejiang, China.
Nucleic Acids Res. 2025 Jan 6;53(D1):D1510-D1515. doi: 10.1093/nar/gkae768.
Proteolysis-targeting chimera (PROTAC) is an emerging therapeutic technology that leverages the ubiquitin-proteasome system to target protein degradation. Due to its event-driven mechanistic characteristics, PROTAC has the potential to regulate traditionally non-druggable targets. Recently, AI-aided drug design has accelerated the development of PROTAC drugs. However, the rational design of PROTACs remains a considerable challenge. Here, we present an updated online database, PROTAC-DB 3.0. In this third version, we have expanded the database to include 6111 PROTACs (87% increase compared to the 2.0 version). Additionally, the database now contains 569 warheads (small molecules targeting the protein), 2753 linkers, and 107 E3 ligands (small molecules recruiting E3 ligases). The number of target-PROTAC-E3 ternary complex structures has also increased to 959. Recognizing the importance of druggability in PROTAC design, we have incorporated pharmacokinetic data to PROTAC-DB 3.0. To enhance user experience, we have added features for sorting based on molecular similarity and literature publication date. PROTAC-DB 3.0 is accessible at http://cadd.zju.edu.cn/protacdb/.
蛋白水解靶向嵌合体（PROTAC）是一种新兴的治疗技术，它利用泛素-蛋白酶体系统来靶向蛋白质降解。由于其事件驱动的机制特性，PROTAC有潜力调节传统上不可成药的靶点。最近，人工智能辅助药物设计加速了PROTAC药物的开发。然而，PROTAC的合理设计仍然是一个巨大的挑战。在此，我们展示了一个更新的在线数据库PROTAC-DB 3.0。在这个第三版中，我们扩展了数据库，纳入了6111个PROTAC（与2.0版本相比增加了87%）。此外，该数据库现在包含569个弹头（靶向蛋白质的小分子）、2753个连接子和107个E3配体（招募E3连接酶的小分子）。靶标-PROTAC-E3三元复合物结构的数量也增加到了959个。认识到成药性在PROTAC设计中的重要性，我们在PROTAC-DB 3.0中纳入了药代动力学数据。为了提升用户体验，我们增加了基于分子相似性和文献发表日期进行排序的功能。可通过http://cadd.zju.edu.cn/protacdb/访问PROTAC-DB 3.0。
