{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:44:03Z","timestamp":1780483443153,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"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":"crossref","award":["82273768"],"award-info":[{"award-number":["82273768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82574254"],"award-info":[{"award-number":["82574254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>PIM kinases, as members of the serine\/threonine kinase family, regulate key cellular processes such as proliferation, apoptosis, and metabolism by phosphorylating multiple substrates, making them important therapeutic targets for cancer treatment. In this study, we reported a series of structurally novel PIM-1 kinase inhibitors based on a scaffold-hopping strategy. After multiple rounds of structural optimization, the highly active compound C2 was obtained, exhibiting an IC50 of 33.02 \u00b1 1.31 nM against PIM-1 kinase. Molecular docking results revealed that compound C2 stably bound to the hydrophobic cavity of the PIM-1 protein and formed hydrogen bond interactions with polar residues in the hinge region, thereby effectively inhibiting kinase activity. In vitro antitumor assessment demonstrated significant proliferation inhibition of the hematological tumor cell line MM.1S (IC50 = 1.87 \u03bcM), comparable to the positive control SGI-1776 (IC50 = 1.71 \u03bcM). In addition, compound C2 possessed favorable drug-like properties and excellent stability in simulated gastrointestinal fluids and rat plasma. This study provides promising lead compounds for the development of novel PIM-1-targeted anticancer drugs, which can be further optimized.<\/jats:p>","DOI":"10.3390\/molecules31040753","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:05:11Z","timestamp":1771855511000},"page":"753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Scaffold Hopping-Guided Design of Novel PIM-1 Inhibitors with Anticancer Activities"],"prefix":"10.3390","volume":"31","author":[{"given":"Yabing","family":"Xin","sequence":"first","affiliation":[{"name":"School of Pharmacy, Suzhou Medical College, Soochow University, Suzhou 215006, China"},{"name":"Jiang Su Key Laboratory of Antibody-Targeted Drug Research, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Suzhou Medical College, Soochow University, Suzhou 215006, China"},{"name":"Jiang Su Key Laboratory of Antibody-Targeted Drug Research, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitong","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Suzhou Medical College, Soochow University, Suzhou 215006, China"},{"name":"Jiang Su Key Laboratory of Antibody-Targeted Drug Research, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Xiao","sequence":"additional","affiliation":[{"name":"Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8587-0122","authenticated-orcid":false,"given":"Qidong","family":"You","sequence":"additional","affiliation":[{"name":"Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1671-1582","authenticated-orcid":false,"given":"Zhengyu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0947-2712","authenticated-orcid":false,"given":"Mengchen","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Suzhou Medical College, Soochow University, Suzhou 215006, China"},{"name":"Jiang Su Key Laboratory of Antibody-Targeted Drug Research, Suzhou 215006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1002\/cncr.33587","article-title":"The ever-increasing importance of cancer as a leading cause of premature death worldwide","volume":"127","author":"Bray","year":"2021","journal-title":"Cancer"},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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