{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:47:11Z","timestamp":1782488831585,"version":"3.54.5"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma, with a substantial proportion of patients developing resistance to standard chemotherapy. Chromosomal translocations resulting in overexpression of the serine\/threonine kinase Proviral Integration site for Moloney murine leukemia virus (PIM-1) contribute to disease progression, therapeutic resistance, and poor clinical outcomes, establishing PIM-1 as a promising molecular target. Unlike many kinases, the ATP-binding site of PIM-1 lacks a backbone hydrogen bond donor within the hinge region due to the presence of Pro123, conferring unique structural features relevant for selective inhibitor design. Although R-CHOP is the first-line treatment for DLBCL, approximately 30%\u201340% of patients develop refractory disease, highlighting the need for novel targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, an in-silico drug repurposing strategy was employed to investigate plerixafor analogues as potential ATP-competitive PIM-1 inhibitors. Quantitative Structure Activity Relationship (QSAR) modeling demonstrated strong predictive performance (R\n                      <jats:sup>2<\/jats:sup>\n                      = 0.82), and molecular docking revealed favorable interactions within the ATP-binding pocket. Molecular dynamics simulations over 200 ns confirmed the dynamic stability of the compound 1\u2013PIM-1 complex, as evidenced by stable Root-Mean Square Deviation (RMSD) values, reduced Root-Mean Square Fluctuation (RMSF) in the active site, and favorable Radius of Gyration (Rg) and Solvent Accessible Surface Area (SASA) profiles.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Additional MM\/GBSA, Principal Component Analysis (PCA), Dynamic Cross-Correlation Matrix (DCCM), and free energy landscape (FEL) analyses further supported complex stability and restricted conformational dynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Collectively, these findings identify plerixafor-derived compound 1 as a promising PIM-1 inhibitor and provide a robust computational framework for the development of targeted therapeutics against aggressive DLBCL, warranting further experimental validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fchem.2026.1798835","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:57:16Z","timestamp":1782485836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational QSAR and structure-based identification of plerixafor-derived PIM-1 kinase inhibitors in diffuse large B-Cell lymphoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Amritha","family":"Thaikkad","sequence":"first","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Angitha","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radul R.","family":"Dev","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bristow Ben","family":"Joseph","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Raju","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhithaj","family":"Jayanandan","sequence":"additional","affiliation":[{"name":"Centre for Integrative Omics Data Science (CIODS), Yenepoya (Deemed to be University)","place":["Mangalore, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34984","DOI":"10.1038\/srep34984","article-title":"Structural insights into conformational stability of both wild-type and mutant EZH2 receptor","volume":"6","author":"Aier","year":"2016","journal-title":"Sci. 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