{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:09:21Z","timestamp":1790629761524,"version":"4.1.0"},"reference-count":188,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019014","name":"Chengdu Municipal Science and Technology Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019014","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Drug discovery plays a crucial role in medicinal chemistry, serving as the cornerstone for developing new treatments to address a wide range of diseases. This review emphasizes the significance of advanced strategies, such as Click Chemistry, Targeted Protein Degradation (TPD), DNA-Encoded Libraries (DELs), and Computer-Aided Drug Design (CADD), in boosting the drug discovery process. Click Chemistry streamlines the synthesis of diverse compound libraries, facilitating efficient hit discovery and lead optimization. TPD harnesses natural degradation pathways to target previously undruggable proteins, while DELs enable high-throughput screening of millions of compounds. CADD employs computational methods to refine candidate selection and reduce resource expenditure. To demonstrate the utility of these methodologies, we highlight exemplary small molecules discovered in the past decade, along with a summary of marketed drugs and investigational new drugs that exemplify their clinical impact. These examples illustrate how these techniques directly contribute to advancing medicinal chemistry from the bench to bedside. Looking ahead, Artificial Intelligence (AI) technologies and interdisciplinary collaboration are poised to address the growing complexity of drug discovery. By fostering a deeper understanding of these transformative strategies, this review aims to inspire innovative research directions and further advance the field of medicinal chemistry.<\/jats:p>","DOI":"10.3389\/fphar.2025.1550158","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T02:06:45Z","timestamp":1739239605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["New strategies to enhance the efficiency and precision of drug discovery"],"prefix":"10.3389","volume":"16","author":[{"given":"Qi","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yalan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1186\/s12915-024-02096-5","article-title":"PharmRL: pharmacophore elucidation with deep geometric reinforcement learning","volume":"22","author":"Aggarwal","year":"2024","journal-title":"BMC Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1186\/s12879-024-09578-5","article-title":"In silico homology modeling of dengue virus non-structural 4B (NS4B) protein and its molecular docking studies using triterpenoids","volume":"24","author":"Ali","year":"2024","journal-title":"BMC. 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