title: Structure-based virtual screening approach to the discovery of p38 MAP kinase inhibitors.
abstract: p38 Mitogen-activated protein kinase (MAPK) has been considered to be a promising target for the development of therapeutics for various immunologic diseases. Herein we report an example for a successful application of the virtual screening with protein-ligand docking to identify the novel inhibitors of p38α MAPK. These inhibitors were screened for having desirable physicochemical properties as a drug candidate and compound 1-3 revealed a moderate inhibitory activity with IC(50) values ranging from 0.7 to 20 μM. Therefore, they deserve a consideration for further development by structure-activity relationship (SAR) studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the newly identified inhibitors in the ATP-binding site of p38 MAPK are addressed in detail.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea.
authors.forename: Hwanho
authors.initials: H
authors.lastname: Choi
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Shin
authors.forename: Hyun Sun
authors.initials: HS
authors.lastname: Ko
authors.forename: Jung Kyun
authors.initials: JK
authors.lastname: Lee
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Hong
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D001665:Binding Sites; D003198:Computer Simulation; D016208:Databases, Factual; D015195:Drug Design; D006801:Humans; D008024:Ligands; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D008024:Ligands; D047428:Protein Kinase Inhibitors; D048308:Mitogen-Activated Protein Kinase 14