{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T21:03:59Z","timestamp":1775077439274,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2020R1A2C2005612"],"award-info":[{"award-number":["2020R1A2C2005612"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["20012892"],"award-info":[{"award-number":["20012892"]}]},{"name":"Technology Innovation Program","award":["2020R1A2C2005612"],"award-info":[{"award-number":["2020R1A2C2005612"]}]},{"name":"Technology Innovation Program","award":["20012892"],"award-info":[{"award-number":["20012892"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Targeting epidermal growth factor receptor (EGFR) mutants is a promising strategy for treating non-small cell lung cancer (NSCLC). This study focused on the computational identification and characterization of potential EGFR mutant-selective inhibitors using pharmacophore design and validation by deep learning, virtual screening, ADMET (Absorption, distribution, metabolism, excretion and toxicity), and molecular docking-dynamics simulations. A pharmacophore model was generated using Pharmit based on the potent inhibitor JBJ-125, which targets the mutant EGFR (PDB 5D41) and is used for the virtual screening of the Zinc database. In total, 16 hits were retrieved from 13,127,550 molecules and 122,276,899 conformers. The pharmacophore model was validated via DeepCoy, generating 100 inactive decoy structures for each active molecule and ADMET tests were conducted using SWISS ADME and PROTOX 3.0. Filtered compounds underwent molecular docking studies using Glide, revealing promising interactions with the EGFR allosteric site along with better docking scores. Molecular dynamics (MD) simulations confirmed the stability of the docked conformations. These results bring out five novel compounds that can be evaluated as single agents or in combination with existing therapies, holding promise for treating the EGFR-mutant NSCLC.<\/jats:p>","DOI":"10.3390\/ph17091107","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:38:43Z","timestamp":1724416723000},"page":"1107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["In Silico Exploration of Novel EGFR Kinase Mutant-Selective Inhibitors Using a Hybrid Computational Approach"],"prefix":"10.3390","volume":"17","author":[{"given":"Md Ali Asif","family":"Noor","sequence":"first","affiliation":[{"name":"Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3912-3695","authenticated-orcid":false,"given":"Md Mazedul","family":"Haq","sequence":"additional","affiliation":[{"name":"Research Center of Bioactive Materials, Department of Bioactive Material Sciences, Division of Life Sciences (Molecular Biology Major), Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1874-3147","authenticated-orcid":false,"given":"Md Arifur Rahman","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Research Center of Bioactive Materials, Department of Bioactive Material Sciences, Division of Life Sciences (Molecular Biology Major), Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5678-3479","authenticated-orcid":false,"given":"Hilal","family":"Tayara","sequence":"additional","affiliation":[{"name":"School of International Engineering and Science, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7437-0140","authenticated-orcid":false,"given":"HyunJoo","family":"Shim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-0001","authenticated-orcid":false,"given":"Kil To","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju 54896, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Fawwaz, M., Mishiro, K., Nishii, R., Sawazaki, I., Shiba, K., Kinuya, S., and Ogawa, K. 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