Virtual Fragment Screening Identification of a Quinoline‐5,8‐dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor |
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| Authors: | Dr Assunta Giordano Federica del?Gaudio Dr Catrine Johansson Prof Raffaele Riccio Prof Udo Oppermann Dr Simone Di?Micco |
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| Affiliation: | 1. Institute of Biomolecular Chemistry (ICB), Consiglio Nazionale delle Ricerche (CNR), Pozzuoli (Napoli), Italy;2. Department of Pharmacy, University of Salerno, Fisciano (Salerno), Italy;3. PhD Program in Drug Discovery and Development, University of Salerno, Fisciano (Salerno), Italy;4. Farmaceutici Damor S.p.A, Naples, Italy;5. Botnar Research Centre, Oxford NIHR BRU, Oxford University, Oxford Centre for Translational Myeloma Research, Oxford, UK;6. Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, Freiburg, Germany |
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| Abstract: | The quinoline‐5,8 dicarboxylic acid scaffold has been identified by a fragment‐based approach as new potential lead compound for the development of JMJD3 inhibitors. Among them, 3‐(2,4‐dimethoxypyrimidin‐5‐yl)quinoline‐5,8‐dicarboxylic acid (compound 3 ) shows low micromolar inhibitory activity against Jumonji domain‐containing protein 3 (JMJD3). The experimental evaluation of inhibitory activity against seven related isoforms of JMJD3 highlighted an unprecedented selectivity toward the biological target of interest. |
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| Keywords: | anticancer agents drug discovery fragment-based approach molecular modeling selective JMJD3 inhibitor |
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