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The potential of proximity\u2010inducing drugs extends beyond targeted protein degradation (TPD), as studies have demonstrated their ability to regulate biological processes such as signal transduction, gene transcription, chromatin regulation, and protein trafficking by modulating protein interaction networks. Rational discovery of proximity\u2010inducing drugs requires clarifying their effects on protein\u2010protein interactions, determining drug selectivity, and developing suitable ligands for drug construction. Proteomics has become a central technology in drug discovery, enabling global identification of the direct drug targets and systematic characterization of proteome\u2010wide downstream responses. This provides a more refined map of drug mechanisms. In parallel, advances in machine learning applied to proteomic data, together with the expansion of proteome\u2010wide ligandability maps, are further accelerating the discovery and optimization of proximity\u2010inducing drugs. This review summarizes recent advances of proximity\u2010inducing drugs, with a particular emphasis on how proteomics facilitates target space expansion, drug efficacy optimization, and ligandability discovery, alongside the emerging contributions of machine learning. Collectively, these insights aim to support the rational development of next\u2010generation proximity\u2010inducing drugs.<\/jats:p>","DOI":"10.1002\/anie.3307512","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:09:42Z","timestamp":1781521782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomics\u2010Driven Strategies for Proximity\u2010Inducing Drug Discovery"],"prefix":"10.1002","volume":"65","author":[{"given":"Rufeng","family":"Fan","sequence":"first","affiliation":[{"name":"Translational Research Institute of Brain and Brain\u2010Like Intelligence, Shanghai Fourth People's Hospital, and Cancer Center, School of Medicine Tongji University Shanghai China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiantian","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Translational Research Institute of Brain and Brain\u2010Like Intelligence, Shanghai Fourth People's Hospital, and Cancer Center, School of Medicine Tongji University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjia","family":"Tan","sequence":"additional","affiliation":[{"name":"Translational Research Institute of Brain and Brain\u2010Like Intelligence, Shanghai Fourth People's Hospital, and Cancer Center, School of Medicine Tongji University Shanghai China"},{"name":"State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao5902"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010023\u201000736\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000729\u20109"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.12.020"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.141230798"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja209924v"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1177319"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244851"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244917"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010020\u20100469\u20101"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2024.12.006"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006348\u20102"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adl5361"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","unstructured":"M. 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