{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T08:27:44Z","timestamp":1778056064253,"version":"3.51.4"},"reference-count":18,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Nature Science Foundation of China","award":["21672031"],"award-info":[{"award-number":["21672031"]}]},{"name":"Fundamental and Advanced Research Projects of Chongqing City","award":["cstc2017jcyjAX0352"],"award-info":[{"award-number":["cstc2017jcyjAX0352"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>As new drugs for the treatment of malignant tumors, transforming growth factor-beta receptor 1 (TGF\u03b2R1) antagonists have attracted wide attention. Based on the crystal structure of TGF\u03b2R1-BMS22 complex, the pharmacophore model A02 with two hydrogen bond acceptors (HBAs) and four hydrophobic (HYD) properties was constructed. From the common features of active ligands reported in the literature, pharmacophore model B10 was also generated, which has two aromatic ring centers (RAs) and two HYD properties. The two models have high sensitivity and specificity to the training set, and they are highly consistent in spatial structure. Combining the two pharmacophore models, two novel skeleton structures with potential activity were selected by virtual screening from the DruglikeDiverse, MiniMaybridge, and ZINC Drug-Like databases. Four compounds (YXY01\u2013YXY04) with potential anti-TGF\u03b2R1 activity were designed based on the new skeleton structures. In combination with Lipinski\u2019s rules; absorption, distribution, metabolism, excretion, and toxicity (ADMET); and, toxicological properties predicted in the study, YXY01-03 with the novel skeleton, good drug-like properties, and potential activity were finally discovered and may have higher safety relative to BMS22, which may be valuable for further research.<\/jats:p>","DOI":"10.3390\/molecules23112824","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T11:55:41Z","timestamp":1540986941000},"page":"2824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel Transforming Growth Factor-Beta Receptor 1 Antagonists through a Pharmacophore-Based Virtual Screening Approach"],"prefix":"10.3390","volume":"23","author":[{"given":"Junhao","family":"Jiang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qihua","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Deng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chongqing Medical University, No. 1 Yixueyuan Rd., Yuzhong District, Chongqing 400016, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"933","DOI":"10.3892\/ijo.2015.2816","article-title":"Role of TGF\u03b2 in regulation of the tumor microenvironment and drug delivery","volume":"46","author":"Papageorgis","year":"2015","journal-title":"Int. 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