{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:59:05Z","timestamp":1787065145628,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    Cyclin\u2010dependent kinase 11 (CDK11) plays a critical role in cell cycle regulation and transcriptional control, making it a promising target for therapeutic intervention in cancer and other proliferative disorders. This study employs computationally driven approaches encompassing homology modelling, molecular dynamic simulations, ultralarge\u2010scale virtual screening and medicinal chemistry optimisation to develop a series of novel inhibitors of CDK11. Our virtual screening pipeline led to the identification of two initial hits (compounds\n                    <jats:bold>3<\/jats:bold>\n                    and\n                    <jats:bold>4<\/jats:bold>\n                    ), which were further evaluated through structure\u2013activity relationship (SAR) studies. Together with structure\u2010guided molecular docking and design, these SAR analyses revealed key structural motifs and functional groups that are crucial for inhibitory activity and selectivity, providing insights into the efficient hit\u2010to\u2010lead optimisation. Compound\n                    <jats:bold>37<\/jats:bold>\n                    emerged as an optimised potent and selective CDK11 inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    4\u2009nM, kinome panel clean). In a lung tumour model, mice dosed twice daily with 100\u2009mg\/kg of compound\n                    <jats:bold>37<\/jats:bold>\n                    showed \u223c30% tumour growth inhibition. Both\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vitro<\/jats:italic>\n                    absorption, distribution, metabolism and excretion and\n                    <jats:italic>in<\/jats:italic>\n                    <jats:italic>vivo<\/jats:italic>\n                    mouse pharmacokinetics (PK) profiling indicated that compound\n                    <jats:bold>37<\/jats:bold>\n                    possesses excellent PK\/pharmacodynamic properties, positioning the compound for further development and evaluation as a lead candidate for CDK11\u2010targeted therapy. Meanwhile, the series of compounds developed throughout this study represent novel tools for studying CDK11\u2010mediated pathophysiology. The integration of in silico modelling, screening and structure\u2010based drug design provides a robust strategy for accelerating the identification of potent and selective inhibitors for other CDK families.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500882","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:51:22Z","timestamp":1774543882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico\u2010Enabled Discovery and Development of Potent and Selective CDK11 Inhibitors"],"prefix":"10.1002","volume":"21","author":[{"given":"Frankie S.","family":"Mak","sequence":"first","affiliation":[{"name":"Experimental Drug Development Centre (EDDC)  Chromos Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fui Mee","family":"Ng","sequence":"additional","affiliation":[{"name":"Experimental Drug Development Centre (EDDC)  Chromos 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