Pub Date : 2026-10-09DOI: 10.1016/j.ejmech.2026.119409
Maryam, Hamza Zahid, Kil To Chong, Hilal Tayara
{"title":"Corrigendum to \"AVP-GPT2: Prompt-conditioned fine-tuning of a GPT-2 protein language model for antiviral peptide identification\" [Eur. J. Med. Chem. 320 (2026) 119352].","authors":"Maryam, Hamza Zahid, Kil To Chong, Hilal Tayara","doi":"10.1016/j.ejmech.2026.119409","DOIUrl":"https://doi.org/10.1016/j.ejmech.2026.119409","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":" ","pages":"119409"},"PeriodicalIF":6.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01DOI: 10.1016/j.ejmech.2026.119384
Brandon Marshall,Edward J.A. Douglas,Kyle D. Perrins,Ebba Qviberg,Maisem Laabei,Michaela Serpi
{"title":"Structural optimization of novel 1,3,4-oxadiazole-based antibacterial compounds for improved stability","authors":"Brandon Marshall,Edward J.A. Douglas,Kyle D. Perrins,Ebba Qviberg,Maisem Laabei,Michaela Serpi","doi":"10.1016/j.ejmech.2026.119384","DOIUrl":"https://doi.org/10.1016/j.ejmech.2026.119384","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"39 1","pages":"119384"},"PeriodicalIF":6.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-10-01DOI: 10.1016/j.ejmech.2026.119400
Zeynep Sude YALCIN,Mehmet Abdullah ALAGOZ,Oztekin ALGUL
{"title":"FROM SINGLE TO DUAL TARGETING: RECENT ADVANCES IN EGFR-BASED DUAL INHIBITORS FOR CANCER THERAPY","authors":"Zeynep Sude YALCIN,Mehmet Abdullah ALAGOZ,Oztekin ALGUL","doi":"10.1016/j.ejmech.2026.119400","DOIUrl":"https://doi.org/10.1016/j.ejmech.2026.119400","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"89 1","pages":"119400"},"PeriodicalIF":6.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-09-23DOI: 10.1016/j.ejmech.2026.119363
Nicolas Moitessier, Mihai Burai-Patrascu
{"title":"Computational small molecule drug design.","authors":"Nicolas Moitessier, Mihai Burai-Patrascu","doi":"10.1016/j.ejmech.2026.119363","DOIUrl":"https://doi.org/10.1016/j.ejmech.2026.119363","url":null,"abstract":"","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":" ","pages":"119363"},"PeriodicalIF":6.7,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><ul><li><span>•</span><span><div>Forty novel heterocyclic pyrimidine compounds were designed, screened, and synthesized using a CADD strategy as highly potent CDK4/6 inhibitors.</div></span></li><li><span>•</span><span><div>The lead compound 3c exhibits potent CDK4/6 kinase inhibitory activity, with an IC50 in the nM range.</div></span></li><li><span>•</span><span><div>Compound 3c induces G1 phase arrest and apoptosis in MCF-7 cancer cells by inhibiting the phosphorylation of the Rb protein.</div></span></li><li><span>•</span><span><div>The lead compound demonstrates good in vivo tumor-suppressing activity and acceptable biosafety, making it worthy of further development.</div></span></li></ul></div><div><div>Cyclin-dependent kinase 4/6 (CDK4/6) plays a pivotal role in cell cycle regulation, and its abnormal activation is closely associated with the initiation and progression of breast cancer.1 However, the limited number of clinically available CDK4/6 inhibitors restricts treatment options. This study focuses on the design, synthesis, and antitumor activity investigation of novel CDK4/6 inhibitors.Employing computer-aided drug design (CADD) strategies and utilizing drug-like and bioisostere principles, we innovatively introduced pyridine-2-aminopyrimidine, thieno[3,2-d]pyrimidine, and pyrazolo[1,5-a]pyrimidine as core skeletal structures to design and screen 250 compound molecules. Based on computational results, including molecular docking and MM/GBSA binding free energy, 40 potential novel CDK4/6 inhibitors were selected for synthesis.Cellular assays validated that compound 3c exhibited the strongest inhibitory activity against CDK4/6 in breast cancer cell lines, with IC<sub>50</sub> values of 0.11 ± 0.01 μM (MCF-7), 0.21 ± 0.01 μM (4T1), and 0.12 ± 0.01 μM (MDA-MB-231). And compound <strong>3c</strong> demonstrated favorable CDK4/6 inhibition rates and showed a certain degree of selectivity among 23 kinases. In vitro mechanistic studies revealed that <strong>3c</strong> consistently inhibited cell colony formation and migration. Furthermore, <strong>3c</strong> effectively arrested the MCF-7 cell cycle at the G1 phase and induced apoptosis. In the MCF-7 xenograft model, compound <strong>3c</strong> achieved a tumor inhibition rate of 45.20%, highlighting its significant potential as a therapeutic CDK4/6 inhibitor.</div></div><div>Cyclin-dependent kinase 4/6 (CDK4/6) plays a pivotal role in cell cycle regulation, and its abnormal activation is closely associated with the initiation and progression of breast cancer.1 However, the limited number of clinically available CDK4/6 inhibitors restricts treatment options. This study focuses on the design, synthesis, and antitumor activity investigation of novel CDK4/6 inhibitors.Employing computer-aided drug design (CADD) strategies and utilizing drug-like and bioisostere principles, we innovatively introduced pyridine-2-aminopyrimidine, thieno[3,2-d]pyrimidine, and pyrazolo[1,5-a]pyrimidine as co
{"title":"CADD-Based Discovery of Novel Heterocyclic Pyrimidine-Based CDK4/6 Inhibitors: Design, Synthesis, and Anti-Breast Cancer Activity Studies","authors":"Xinya Lv , Xiaoling Huang , Lulu Tian , Shidi Xu , Yujie Zhan , Hanrui Hou , Dajun Zhang , Linxiao Wang , Shan Xu","doi":"10.1016/j.ejmech.2026.118932","DOIUrl":"10.1016/j.ejmech.2026.118932","url":null,"abstract":"<div><ul><li><span>•</span><span><div>Forty novel heterocyclic pyrimidine compounds were designed, screened, and synthesized using a CADD strategy as highly potent CDK4/6 inhibitors.</div></span></li><li><span>•</span><span><div>The lead compound 3c exhibits potent CDK4/6 kinase inhibitory activity, with an IC50 in the nM range.</div></span></li><li><span>•</span><span><div>Compound 3c induces G1 phase arrest and apoptosis in MCF-7 cancer cells by inhibiting the phosphorylation of the Rb protein.</div></span></li><li><span>•</span><span><div>The lead compound demonstrates good in vivo tumor-suppressing activity and acceptable biosafety, making it worthy of further development.</div></span></li></ul></div><div><div>Cyclin-dependent kinase 4/6 (CDK4/6) plays a pivotal role in cell cycle regulation, and its abnormal activation is closely associated with the initiation and progression of breast cancer.1 However, the limited number of clinically available CDK4/6 inhibitors restricts treatment options. This study focuses on the design, synthesis, and antitumor activity investigation of novel CDK4/6 inhibitors.Employing computer-aided drug design (CADD) strategies and utilizing drug-like and bioisostere principles, we innovatively introduced pyridine-2-aminopyrimidine, thieno[3,2-d]pyrimidine, and pyrazolo[1,5-a]pyrimidine as core skeletal structures to design and screen 250 compound molecules. Based on computational results, including molecular docking and MM/GBSA binding free energy, 40 potential novel CDK4/6 inhibitors were selected for synthesis.Cellular assays validated that compound 3c exhibited the strongest inhibitory activity against CDK4/6 in breast cancer cell lines, with IC<sub>50</sub> values of 0.11 ± 0.01 μM (MCF-7), 0.21 ± 0.01 μM (4T1), and 0.12 ± 0.01 μM (MDA-MB-231). And compound <strong>3c</strong> demonstrated favorable CDK4/6 inhibition rates and showed a certain degree of selectivity among 23 kinases. In vitro mechanistic studies revealed that <strong>3c</strong> consistently inhibited cell colony formation and migration. Furthermore, <strong>3c</strong> effectively arrested the MCF-7 cell cycle at the G1 phase and induced apoptosis. In the MCF-7 xenograft model, compound <strong>3c</strong> achieved a tumor inhibition rate of 45.20%, highlighting its significant potential as a therapeutic CDK4/6 inhibitor.</div></div><div>Cyclin-dependent kinase 4/6 (CDK4/6) plays a pivotal role in cell cycle regulation, and its abnormal activation is closely associated with the initiation and progression of breast cancer.1 However, the limited number of clinically available CDK4/6 inhibitors restricts treatment options. This study focuses on the design, synthesis, and antitumor activity investigation of novel CDK4/6 inhibitors.Employing computer-aided drug design (CADD) strategies and utilizing drug-like and bioisostere principles, we innovatively introduced pyridine-2-aminopyrimidine, thieno[3,2-d]pyrimidine, and pyrazolo[1,5-a]pyrimidine as co","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"315 ","pages":"Article 118932"},"PeriodicalIF":5.9,"publicationDate":"2026-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147999287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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