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To verify the effectiveness of selecting a tractable number of candidates from a compound library using cofolding models, we strove to identify a novel inhibitory active compound using Boltz-2, a representative cofolding model, for aldo-keto reductase 1B10 (AKR1B10), which is highly expressed in various cancers. Consequently, of the 40 candidate compounds obtained after narrowing-down 867 candidates from a chemically diverse library based on prediction results by Boltz-2 and candidate selection with sufficient diversity, 70% (28 of 40 tested) compounds at IC50 &amp;lt; 10 \u03bcM were found to have inhibitory activity and to provide identification of multiple submicromolar inhibitors exhibiting novel scaffolds. Our results demonstrate that our sparse selection approach using Boltz-2 is helpful for enhancing AI-driven drug discovery. Moreover, the findings highlight its potential applicability for translating AI-generated predictions into experimentally actionable hits.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c00874","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T15:02:09Z","timestamp":1789225329000},"page":"12100-12114","source":"Crossref","is-referenced-by-count":0,"title":["Efficient Discovery\nof Potent AKR1B10 Inhibitors Using\nCo-folding Model Boltz-2"],"prefix":"10.1021","volume":"66","author":[{"given":"Shinya","family":"Kawano","sequence":"first","affiliation":[{"name":"Gifu Pharmaceutical University , , , ,","place":["Gifu, Gifu, Japan, 501-1196"]},{"name":"National Institute of Advanced Industrial Science and Technology (AIST) , , , ,","place":["Tokyo, Koto-ku, Japan, 135-0064"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ikari","sequence":"additional","affiliation":[{"name":"Gifu Pharmaceutical University , , , ,","place":["Gifu, Gifu, Japan, 501-1196"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Endo","sequence":"additional","affiliation":[{"name":"Gifu University , , , ,","place":["Gifu, Gifu, Japan, 501-1194"]},{"name":"Gifu University , , , ,","place":["Gifu, Gifu, Japan, 501-1193"]},{"name":"Gifu University , , , ,","place":["Gifu, Gifu, Japan, 501-1193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4567-4768","authenticated-orcid":true,"given":"Kentaro","family":"Tomii","sequence":"additional","affiliation":[{"name":"National Institute of Advanced Industrial Science and Technology (AIST) , , , ,","place":["Tokyo, Koto-ku, Japan, 135-0064"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2026092810071844700_cit1","doi-asserted-by":"publisher","first-page":"2210.01776","DOI":"10.48550\/arXiv.2210.01776","article-title":"DiffDock:\nDiffusion Steps, Twists, and Turns for Molecular Docking","author":"Corso","year":"2022","journal-title":"arXiv"},{"key":"2026092810071844700_cit2","unstructured":"I.., Labs\n          : Alphafold 3\npredicts the structure and interactions of all of life\u2019s molecules, 2024. https:\/\/www.isomorphiclabs.com\/articles\/alphafold-3-predicts-the-structure-and-interactions-of-all-of-lifes-molecules. 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