title: Identification of novel inhibitors of mitogen-activated protein kinase phosphatase-1 with structure-based virtual screening.
abstract: Mitogen-activated protein kinase phosphatase-1 (MKP-1) has proved to be an attractive target for the development of therapeutics for the treatment of cancer. We report the first example for a successful application of the structure-based virtual screening to identify the novel inhibitors of MKP-1. It is shown that the efficiency of virtual screening can be enhanced significantly by the incorporation of a new solvation energy term in the scoring function. The newly found inhibitors have desirable physicochemical properties as a drug candidate and reveal a moderate potency with IC(50) values ranging from 20 to 50 μM. Therefore, they deserve a consideration for further development by structure-activity relationship studies to optimize the inhibitory activities. Structural features relevant to the stabilization of the inhibitors in the active site of MKP-1 are discussed in detail.
authors.affiliation: Department of Bioscience and Biotechnology, Sejong University, Kunja-Dong, Kwangjin-Ku, Seoul, Korea. hspark@sejong.ac.kr
authors.forename: Hwangseo
authors.initials: H
authors.lastname: Park
authors.forename: Jeong-Yi
authors.initials: JY
authors.lastname: Jeon
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Kim
authors.forename: Dae Gwin
authors.initials: DG
authors.lastname: Jeong
authors.forename: Seong Eon
authors.initials: SE
authors.lastname: Ryu
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D054638:Dual Specificity Phosphatase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000737:chemistry; D020128:Inhibitory Concentration 50; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1