{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T15:10:46Z","timestamp":1788189046058,"version":"build-2803163510"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T00:00:00Z","timestamp":1650499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002457","name":"Chosun University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002457","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>JAK1 plays a significant role in the intracellular signaling by interacting with cytokine receptors in different types of cells and is linked to the pathogenesis of various cancers and in the pathology of the immune system. In this study, ligand-based pharmacophore modeling combined with virtual screening and molecular docking methods was incorporated to identify the potent and selective lead compounds for JAK1. Initially, the ligand-based pharmacophore models were generated using a set of 52 JAK1 inhibitors named C-2 methyl\/hydroxyethyl imidazopyrrolopyridines derivatives. Twenty-seven pharmacophore models with five and six pharmacophore features were generated and validated using potency and selectivity validation methods. During potency validation, the Guner-Henry score was calculated to check the accuracy of the generated models, whereas in selectivity validation, the pharmacophore models that are capable of identifying selective JAK1 inhibitors were evaluated. Based on the validation results, the best pharmacophore models ADHRRR, DDHRRR, DDRRR, DPRRR, DHRRR, ADRRR, DDHRR, and ADPRR were selected and taken for virtual screening against the Maybridge, Asinex, Chemdiv, Enamine, Lifechemicals, and Zinc database to identify the new molecules with novel scaffold that can bind to JAK1. A total of 4,265 hits were identified from screening and checked for acceptable drug-like properties. A total of 2,856 hits were selected after ADME predictions and taken for Glide molecular docking to assess the accurate binding modes of the lead candidates. Ninety molecules were shortlisted based on binding energy and H-bond interactions with the important residues of JAK1. The docking results were authenticated by calculating binding free energy for protein\u2013ligand complexes using the MM-GBSA calculation and induced fit docking methods. Subsequently, the cross-docking approach was carried out to recognize the selective JAK1 lead compounds. Finally, top five lead compounds that were potent and selective against JAK1 were selected and validated using molecular dynamics simulation. Besides, the density functional theory study was also carried out for the selected leads. Through various computational studies, we observed good potency and selectivity of these lead compounds when compared with the drug ruxolitinib. Compounds such as T5923555 and T5923531 were found to be the best and can be further validated using <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> methods.<\/jats:p>","DOI":"10.3389\/fphar.2022.837369","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T05:01:20Z","timestamp":1650517280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":30,"title":["Identification of Potent and Selective JAK1 Lead Compounds Through Ligand-Based Drug Design Approaches"],"prefix":"10.3389","volume":"13","author":[{"given":"Sathya","family":"Babu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santhosh Kumar","family":"Nagarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sruthy","family":"Sathish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vir Singh","family":"Negi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglae","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirumurthy","family":"Madhavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.molstruc.2015.08.031","article-title":"Identification of Leads through In Silico Approaches Utilizing Benzylthio-1h-Benzo[d]imidazol-1-Yl Acetic Acid Derivatives: A Potent CRTh2 Antagonist","volume":"1102","author":"Babu","year":"2015","journal-title":"J. Mol. Struct."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1063\/1.476722","article-title":"A New Inhomogeneity Parameter in Density-Functional Theory","volume":"109","author":"Becke","year":"1998","journal-title":"J. Chem. Phys."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12258","DOI":"10.1038\/ncomms12258","article-title":"Decreased NK-Cell Tumour Immunosurveillance Consequent to JAK Inhibition Enhances Metastasis in Breast Cancer Models","volume":"7","author":"Bottos","year":"2016","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1107\/S2053230X16016356","article-title":"Development of a High-Throughput crystal Structure-Determination Platform for JAK1 Using a Novel Metal-Chelator Soaking System","volume":"72","author":"Caspers","year":"2016","journal-title":"Acta Crystallogr. F Struct. Biol. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"6625","DOI":"10.2147\/CMAR.S201342","article-title":"HOXA10 Deteriorates Gastric Cancer through Activating JAK1\/STAT3 Signaling Pathway","volume":"11","author":"Chen","year":"2019","journal-title":"Cancer Manag. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.jmb.2010.05.020","article-title":"Structural and Thermodynamic Characterization of the TYK2 and JAK3 Kinase Domains in Complex with CP-690550 and CMP-6","volume":"400","author":"Chrencik","year":"2010","journal-title":"J. Mol. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2851","DOI":"10.1021\/ci900320p","article-title":"Prediction of Potency of Protease Inhibitors Using Free Energy Simulations with Polarizable Quantum Mechanics-Based Ligand Charges and a Hybrid Water Model","volume":"49","author":"Das","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"B9","doi-asserted-by":"publisher","first-page":"4969","DOI":"10.1016\/j.bmcl.2014.09.031","article-title":"Scaffold Hopping towards Potent and Selective JAK3 Inhibitors: Discovery of Novel C-5 Substituted Pyrrolopyrazines","volume":"24","author":"De Vicente","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B10","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s10822-006-9087-6","article-title":"PHASE: a New Engine for Pharmacophore Perception, 3D QSAR Model Development, and 3D Database Screening: 1. Methodology and Preliminary Results","volume":"20","author":"Dixon","year":"2006","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"B11","doi-asserted-by":"publisher","first-page":"5721","DOI":"10.1016\/j.bmcl.2014.10.061","article-title":"Discovery of Pyrrolo[1,2-B]pyridazine-3-Carboxamides as Janus Kinase (JAK) Inhibitors","volume":"24","author":"Duan","year":"2014","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5243","DOI":"10.1021\/jm300248q","article-title":"A Selective, Orally Bioavailable 1,2,4-Triazolo[1,5-A]pyridine-Based Inhibitor of Janus Kinase 2 for Use in Anticancer Therapy: Discovery of CEP-33779","volume":"55","author":"Dugan","year":"2012","journal-title":"J. Med. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7653","DOI":"10.1016\/j.bmcl.2012.10.007","article-title":"SAR and In Vivo Evaluation of 4-Aryl-2-Aminoalkylpyrimidines as Potent and Selective Janus Kinase 2 (JAK2) Inhibitors","volume":"22","author":"Forsyth","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra Precision glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein-Ligand Complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1042\/BJ20100774","article-title":"Transforming JAK1 Mutations Exhibit Differential Signalling, FERM Domain Requirements and Growth Responses to Interferon-\u03b3","volume":"432","author":"Gordon","year":"2010","journal-title":"Biochem. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.immuni.2020.07.006","article-title":"Complex Autoinflammatory Syndrome Unveils Fundamental Principles of JAK1 Kinase Transcriptional and Biochemical Function","volume":"53","author":"Gruber","year":"2020","journal-title":"Immunity"},{"key":"B17","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1002\/(sici)1099-1352(199603)9:2<175::aid-jmr260>3.0.co;2-d","article-title":"Molecular Docking towards Drug Discovery","volume":"9","author":"Gschwend","year":"1996","journal-title":"J. Mol. Recognit"},{"key":"B18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/j.1582-4934.2010.01018.x","article-title":"Perspectives for the Use of Structural Information and Chemical Genetics to Develop Inhibitors of Janus Kinases","volume":"14","author":"Haan","year":"2010","journal-title":"J. Cel Mol. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.chembiol.2011.01.012","article-title":"Jak1 Has a Dominant Role over Jak3 in Signal Transduction through \u03b3c-containing Cytokine Receptors","volume":"18","author":"Haan","year":"2011","journal-title":"Chem. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: a New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/j.bmcl.2011.01.022","article-title":"Pyrrolo[1,2-f]triazines as JAK2 Inhibitors: Achieving Potency and Selectivity for JAK2 over JAK3","volume":"21","author":"Harikrishnan","year":"2011","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B22","first-page":"1347","article-title":"JAK2, a Third Member of the JAK Family of Protein Tyrosine Kinases","volume":"7","author":"Harpur","year":"1992","journal-title":"Oncogene"},{"key":"B23","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1021\/ci800293n","article-title":"Validation of Molecular Docking Programs for Virtual Screening against Dihydropteroate Synthase","volume":"49","author":"Hevener","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"B24","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1002\/minf.201100135","article-title":"Free Energy Calculations by the Molecular Mechanics Poisson-Boltzmann Surface Area Method","volume":"31","author":"Homeyer","year":"2012","journal-title":"Mol. Inform."},{"key":"B25","doi-asserted-by":"publisher","first-page":"845","DOI":"10.3324\/haematol.2010.036350","article-title":"Oncogenic JAK1 and JAK2-Activating Mutations Resistant to ATP-Competitive Inhibitors","volume":"96","author":"Hornakova","year":"2011","journal-title":"Haematologica"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3592","DOI":"10.1016\/j.bmcl.2013.04.018","article-title":"Novel Triazolo-Pyrrolopyridines as Inhibitors of Janus Kinase 1","volume":"23","author":"Hurley","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B27","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1021\/jm1011319","article-title":"Discovery of 5-Chloro-N2-[(1s)-1-(5-Fluoropyrimidin-2-Yl)ethyl]-N4-(5-Methyl-1h-Pyrazol-3-Yl)pyrimidine-2,4-Diamine (AZD1480) as a Novel Inhibitor of the Jak\/Stat Pathway","volume":"54","author":"Ioannidis","year":"2011","journal-title":"J. Med. Chem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC--a Free Database of Commercially Available Compounds for Virtual Screening","volume":"45","author":"Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1021\/ci3001277","article-title":"ZINC: a Free Tool to Discover Chemistry for Biology","volume":"52","author":"Irwin","year":"2012","journal-title":"J. Chem. Inf. Model."},{"key":"B30","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1080\/10799893.2017.1328442","article-title":"Molecular Modeling-Driven Approach for Identification of Janus Kinase 1 Inhibitors through 3D-QSAR, Docking and Molecular Dynamics Simulations","volume":"37","author":"Itteboina","year":"2017","journal-title":"J. Recept Signal. Transduct Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A Hierarchical Approach to All-Atom Protein Loop Prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1016\/j.bmcl.2013.03.015","article-title":"Discovery of a Series of Novel 5H-Pyrrolo[2,3-B]pyrazine-2-Phenyl Ethers, as Potent JAK3 Kinase Inhibitors","volume":"23","author":"Jaime-Figueroa","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B33","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1021\/jm020406h","article-title":"Surflex: Fully Automatic Flexible Molecular Docking Using a Molecular Similarity-Based Search Engine","volume":"46","author":"Jain","year":"2003","journal-title":"J. Med. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/s0169-409x(02)00008-x","article-title":"Prediction of Drug Solubility from Structure","volume":"54","author":"Jorgensen","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"B35","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1080\/07391102.2020.1714483","article-title":"Molecular Modeling Studies of Pyrrolo[2,3-D]pyrimidin-4-Amine Derivatives as JAK1 Inhibitors Based on 3D-QSAR, Molecular Docking, Molecular Dynamics (MD) and MM-PBSA Calculations","volume":"39","author":"Keretsu","year":"","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B36","doi-asserted-by":"publisher","first-page":"23051","DOI":"10.1038\/s41598-021-0236410.1038\/s41598-021-02364-2","article-title":"Computer Aided Designing of Novel Pyrrolopyridine Derivatives as JAK1 Inhibitors","volume":"11","author":"Keretsu","year":"","journal-title":"Sci. Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"46153","DOI":"10.1038\/srep46153","article-title":"Suppressor of Cytokine Signaling 2 Negatively Regulates NK Cell Differentiation by Inhibiting JAK2 Activity","volume":"7","author":"Kim","year":"2017","journal-title":"Sci. Rep."},{"key":"B38","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.stem.2017.08.011","article-title":"Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis","volume":"21","author":"Kleppe","year":"2017","journal-title":"Cell stem cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"5901","DOI":"10.1021\/jm300438j","article-title":"Identification of Imidazo-Pyrrolopyridines as Novel and Potent JAK1 Inhibitors","volume":"55","author":"Kulagowski","year":"2012","journal-title":"J. Med. Chem."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3081","DOI":"10.1080\/07391102.2018.1508368","article-title":"Toward a Better Understanding of the Interaction between Somatostatin Receptor 2 and its Ligands: a Structural Characterization Study Using Molecular Dynamics and Conceptual Density Functional Theory","volume":"37","author":"Kumar Nagarajan","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1021\/ci500020m","article-title":"g_mmpbsa-A GROMACS Tool for High-Throughput MM-PBSA Calculationsg_mmpbsa-Aa GROMACS Tool for High-Throughput MM-PBSA Calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J. Chem. Inf. Model."},{"key":"B42","doi-asserted-by":"publisher","first-page":"5923","DOI":"10.1016\/j.bmcl.2013.08.082","article-title":"Design and Evaluation of Novel 8-Oxo-Pyridopyrimidine Jak1\/2 Inhibitors","volume":"23","author":"Labadie","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"7627","DOI":"10.1016\/j.bmcl.2012.10.008","article-title":"Structure-based Discovery of C-2 Substituted Imidazo-Pyrrolopyridine JAK1 Inhibitors with Improved Selectivity over JAK2","volume":"22","author":"Labadie","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1002\/prot.23106","article-title":"The VSGB 2.0 Model: a Next Generation Energy Model for High Resolution Protein Structure Modeling","volume":"79","author":"Li","year":"2011","journal-title":"Proteins"},{"key":"B45","doi-asserted-by":"publisher","first-page":"418767","DOI":"10.1155\/2015\/418767","article-title":"In Silico Design of Human IMPDH Inhibitors Using Pharmacophore Mapping and Molecular Docking Approaches","volume":"2015","author":"Li","year":"2015","journal-title":"Comput. Math. Methods Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S1056-8719(00)00107-6","article-title":"Drug-like Properties and the Causes of Poor Solubility and Poor Permeability","volume":"44","author":"Lipinski","year":"2000","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"B47","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1134\/S0026893308040195","article-title":"Radius of Gyration Is Indicator of Compactness of Protein Structure","volume":"42","author":"Lobanov","year":"2008","journal-title":"Mol. Biol. (Mosk)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.bmcl.2006.09.055","article-title":"Farnesyltransferase Pharmacophore Model Derived from Diverse Classes of Inhibitors","volume":"17","author":"Lu","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B49","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1182\/blood-2005-06-2413","article-title":"The Structural Basis of Janus Kinase 2 Inhibition by a Potent and Specific Pan-Janus Kinase Inhibitor","volume":"107","author":"Lucet","year":"2006","journal-title":"Blood"},{"key":"B50","first-page":"1187","article-title":"Induced-fit Docking and Virtual Screening for 8-Hydroxy-3-Methoxy- 5H-Pyrido [2,1-c] Pyrazin-5-One Derivatives as Inducible Nitric Oxide Synthase Inhibitors","volume":"6","author":"Luo","year":"2014","journal-title":"J. Chem. Pharm. Res."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2793","DOI":"10.1016\/j.bmcl.2013.02.012","article-title":"Strategic Use of Conformational Bias and Structure Based Design to Identify Potent JAK3 Inhibitors with Improved Selectivity against the JAK Family and the Kinome","volume":"23","author":"Lynch","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B52","doi-asserted-by":"publisher","first-page":"4805","DOI":"10.1021\/jm060522a","article-title":"Accurate Prediction of the Relative Potencies of Members of a Series of Kinase Inhibitors Using Molecular Docking and MM-GBSA Scoring","volume":"49","author":"Lyne","year":"2006","journal-title":"J. Med. Chem."},{"key":"B53","doi-asserted-by":"publisher","first-page":"203","DOI":"10.4155\/fmc.14.149","article-title":"Progress toward JAK1-Selective Inhibitors","volume":"7","author":"Menet","year":"2015","journal-title":"Future Med. Chem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"6582","DOI":"10.1021\/jm300687e","article-title":"Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking","volume":"55","author":"Mysinger","year":"2012","journal-title":"J. Med. Chem."},{"key":"B55","volume-title":"Protein JAK Makes Cancer Cells Contract, So They Can Squeeze Out of a Tumor","author":"Nordqvist","year":"2011"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2609","DOI":"10.1016\/j.bmcl.2010.02.056","article-title":"Discovery and SAR of Potent, Orally Available 2,8-Diaryl-Quinoxalines as a New Class of JAK2 inhibitorsDiscovery and SAR of Potent, Orally Available 2, 8-Diaryl-Quinoxalines as a New Class of JAK2 Inhibitors","volume":"20","author":"Pissot-Soldermann","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B57","doi-asserted-by":"publisher","first-page":"800","DOI":"10.3390\/cancers13040800","article-title":"Janus Kinases in Leukemia","volume":"13","author":"Raivola","year":"2021","journal-title":"Cancers"},{"key":"B58","doi-asserted-by":"publisher","first-page":"329","DOI":"10.2174\/138920307781369427","article-title":"Virtual Screening in Drug Discovery -- a Computational Perspective","volume":"8","author":"Reddy","year":"2007","journal-title":"Curr. Protein Pept. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"e00612","DOI":"10.1016\/j.heliyon.2018.e00612","article-title":"Discovery of Small Molecules through Pharmacophore Modeling, Docking and Molecular Dynamics Simulation against Plasmodium Vivax Vivapain-3 (VP-3)","volume":"4","author":"Saddala","year":"2018","journal-title":"Heliyon"},{"key":"B60","doi-asserted-by":"publisher","first-page":"47954","DOI":"10.1074\/jbc.M205156200","article-title":"The Pseudokinase Domain Is Required for Suppression of Basal Activity of Jak2 and Jak3 Tyrosine Kinases and for Cytokine-Inducible Activation of Signal Transduction","volume":"277","author":"Saharinen","year":"2002","journal-title":"J. Biol. Chem."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1016\/j.ejmech.2010.01.016","article-title":"3D QSAR Pharmacophore Based Virtual Screening and Molecular Docking for Identification of Potential HSP90 Inhibitors","volume":"45","author":"Sakkiah","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.5012\/bkcs.2009.30.5.1152","article-title":"Pharmacophore Mapping and Virtual Screening for SIRT1 Activators","volume":"30","author":"Sakkiah","year":"2009","journal-title":"Bull. Korean Chem. Soc."},{"key":"B63","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.molstruc.2010.08.050","article-title":"Identification of Critical Chemical Features for Aurora Kinase-B Inhibitors Using Hip-Hop, Virtual Screening and Molecular Docking","volume":"985","author":"Sakkiah","year":"2011","journal-title":"J. Mol. Struct."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1007\/s00044-014-1223-6","article-title":"Computational Identification of JAK2 Inhibitors: a Combined Pharmacophore Mapping and Molecular Docking Approach","volume":"24","author":"Sathe","year":"2014","journal-title":"Med. Chem. Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"8440","DOI":"10.1021\/jm200911r","article-title":"Discovery of Potent and Highly Selective Thienopyridine Janus Kinase 2 Inhibitors","volume":"54","author":"Schenkel","year":"2011","journal-title":"J. Med. Chem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1158\/0008-5472.CAN-14-3198","article-title":"JAK Inhibition Impairs NK Cell Function in Myeloproliferative Neoplasms","volume":"75","author":"Sch\u00f6nberg","year":"2015","journal-title":"Cancer Res."},{"key":"B67","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nrd.2017.20110.1038\/nrd.2017.267","article-title":"JAK Inhibition as a Therapeutic Strategy for Immune and Inflammatory Diseases","volume":"17","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.4049\/jimmunol.1202859","article-title":"A Restricted Role for TYK2 Catalytic Activity in Human Cytokine Responses Revealed by Novel TYK2-Selective Inhibitors","volume":"191","author":"Sohn","year":"2013","journal-title":"J. Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1021\/jm301646k","article-title":"3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and In Vivo Models","volume":"56","author":"Soth","year":"2013","journal-title":"J. Med. Chem."},{"key":"B70","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.drudis.2006.02.008","article-title":"Integrating Molecular Design Resources within Modern Drug Discovery Research: the Roche Experience","volume":"11","author":"Stahl","year":"2006","journal-title":"Drug Discov. Today"},{"key":"B71","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1021\/acs.jcim.5b00559","article-title":"ZINC 15--Ligand Discovery for Everyone","volume":"55","author":"Sterling","year":"2015","journal-title":"J. Chem. Inf. Model."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/j.bmc.2007.10.076","article-title":"Discovery of New MurF Inhibitors via Pharmacophore Modeling and QSAR Analysis Followed by In-Silico Screening","volume":"16","author":"Taha","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"B73","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3390\/ph15010030","article-title":"Molecular Modeling Insights into Upadacitinib Selectivity upon Binding to JAK Protein Family","volume":"15","author":"Taldaev","year":"2022","journal-title":"Pharmaceuticals"},{"key":"B74","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1021\/jm101157q","article-title":"Identification of a Potent Janus Kinase 3 Inhibitor with High Selectivity within the Janus Kinase Family","volume":"54","author":"Thoma","year":"2011","journal-title":"J. Med. Chem."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1021\/acs.jmedchem.7b01598","article-title":"Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases","volume":"61","author":"Vazquez","year":"2018","journal-title":"J. Med. Chem."},{"key":"B76","doi-asserted-by":"publisher","first-page":"333","DOI":"10.3797\/scipharm.0803-03","article-title":"Virtual Screening: a Fast Tool for Drug Design","volume":"76","author":"Vyas","year":"2008","journal-title":"Sci. Pharm."},{"key":"B77","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.jmgm.2008.09.002","article-title":"Induced-fit Docking of Mometasone Furoate and Further Evidence for Glucocorticoid Receptor 17alpha Pocket Flexibility","volume":"27","author":"Wang","year":"2008","journal-title":"J. Mol. Graph Model."},{"key":"B78","doi-asserted-by":"publisher","first-page":"4972","DOI":"10.1016\/j.bmcl.2008.08.033","article-title":"Pharmacophore Modeling and Virtual Screening for Designing Potential PLK1 Inhibitors","volume":"18","author":"Wang","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B79","doi-asserted-by":"publisher","first-page":"7938","DOI":"10.1021\/jm901383u","article-title":"Janus Kinase 2 Inhibitors. Synthesis and Characterization of a Novel Polycyclic Azaindole","volume":"52","author":"Wang","year":"2009","journal-title":"J. Med. Chem."},{"key":"B80","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1158\/1535-7163.MCT-14-0077","article-title":"Targeting JAK1\/STAT3 Signaling Suppresses Tumor Progression and Metastasis in a Peritoneal Model of Human Ovarian Cancer","volume":"13","author":"Wen","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"B81","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jmb.2009.01.041","article-title":"Dissecting Specificity in the Janus Kinases: the Structures of JAK-specific Inhibitors Complexed to the JAK1 and JAK2 Protein Tyrosine Kinase Domains","volume":"387","author":"Williams","year":"2009","journal-title":"J. Mol. Biol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"4809","DOI":"10.1182\/blood-2007-05-090308","article-title":"Identification of Somatic JAK1 Mutations in Patients with Acute Myeloid Leukemia","volume":"111","author":"Xiang","year":"2008","journal-title":"Blood"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1016\/j.bmcl.2009.02.049","article-title":"Pharmacophore Modeling Study Based on Known Spleen Tyrosine Kinase Inhibitors Together with Virtual Screening for Identifying Novel Inhibitors","volume":"19","author":"Xie","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1111\/jcmm.16289","article-title":"Anwulignan Is a Novel JAK1 Inhibitor that Suppresses Non-small Cell Lung Cancer Growth","volume":"25","author":"Xie","year":"2021","journal-title":"J. Cel Mol Med"},{"key":"B85","doi-asserted-by":"publisher","first-page":"13709","DOI":"10.1021\/ja9039373","article-title":"Importance of Ligand Reorganization Free Energy in Protein-Ligand Binding-Affinity Prediction","volume":"131","author":"Yang","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"B86","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.bmcl.2006.10.062","article-title":"Simplified Staurosporine Analogs as Potent JAK3 Inhibitors","volume":"17","author":"Yang","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B87","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3892\/or.17.1.35","article-title":"Altered P-JAK1 Expression Is Associated with Estrogen Receptor Status in Breast Infiltrating Ductal Carcinoma","volume":"17","author":"Yeh","year":"2007","journal-title":"Oncol. Rep."},{"key":"B88","doi-asserted-by":"publisher","first-page":"4764","DOI":"10.1021\/jm4004895","article-title":"Identification of C-2 Hydroxyethyl Imidazopyrrolopyridines as Potent JAK1 Inhibitors with Favorable Physicochemical Properties and High Selectivity over JAK2","volume":"56","author":"Zak","year":"2013","journal-title":"J. Med. Chem."},{"key":"B89","doi-asserted-by":"publisher","first-page":"6176","DOI":"10.1021\/jm300628c","article-title":"Discovery and Optimization of C-2 Methyl Imidazopyrrolopyridines as Potent and Orally Bioavailable JAK1 Inhibitors with Selectivity over JAK2","volume":"55","author":"Zak","year":"2012","journal-title":"J. Med. Chem."},{"key":"B90","doi-asserted-by":"publisher","first-page":"4184","DOI":"10.1021\/jp0225774","article-title":"Ionization Potential, Electron Affinity, Electronegativity, Hardness, and Electron Excitation Energy: Molecular Properties from Density Functional Theory Orbital Energies","volume":"107","author":"Zhan","year":"2003","journal-title":"J. Phys. Chem. A."},{"key":"B91","doi-asserted-by":"publisher","first-page":"7022","DOI":"10.3390\/ijms12107022","article-title":"Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on \u03b1(1A)-adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment","volume":"12","author":"Zhao","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"B92","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1016\/j.jmgm.2009.08.012","article-title":"Induced-fit Docking Studies of the Active and Inactive States of Protein Tyrosine Kinases","volume":"28","author":"Zhong","year":"2009","journal-title":"J. Mol. Graph Model."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.837369\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T05:01:27Z","timestamp":1650517287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.837369\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,21]]},"references-count":92,"alternative-id":["10.3389\/fphar.2022.837369"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.837369","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,21]]},"article-number":"837369"}}