title: Finding new scaffolds of JAK3 inhibitors in public database: 3D-QSAR models & shape-based screening.
abstract: The STAT/JAK3 pathway is a well-known therapeutic target in various diseases (ex. rheumatoid arthritis and psoriasis). The therapeutic advantage of JAK3 inhibition motivated to find new scaffolds with desired DMPK. For the purpose, in silico high-throughput sieves method is developed consisting of a receptor-guided three-dimensional quantitative structure-activity relationship study and shape-based virtual screening. We developed robust and predictive comparative molecular field analysis (q (2) = 0.760, r (2) = 0.915) and comparative molecular similarity index analysis (q (2) = 0.817, r (2) = 0.981) models and validated these using a test set, which produced satisfactory predictions of 0.925 and 0.838, respectively.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon, Republic of Korea.|Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Changdev G
authors.initials: CG
authors.lastname: Gadhe
authors.affiliation: Department of Pharmacy, College of Pharmacy, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon, Republic of Korea.|Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon, Republic of Korea.
authors.forename: Eunhee
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, College of Pharmacy, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Incheon, Republic of Korea. kmh0515@gachon.ac.kr.|Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon, Republic of Korea. kmh0515@gachon.ac.kr.
authors.forename: Mi-Hyun
authors.initials: MH
authors.lastname: Kim
mesh_terms: D003198:Computer Simulation; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D050791:STAT Transcription Factors; C507933:JAK3 protein, human; D053616:Janus Kinase 3
keywords: 3D-QSAR; Anti-inflammatory; Diversity of scaffolds; JAK3 inhibitors; Shape-based screening