title: Discovery of novel PRL-3 inhibitors based on the structure-based virtual screening.
abstract: The inhibitors of phosphatase of regenerating liver-3 (PRL-3) have been shown to be useful as therapeutics for the treatment of cancer. We have been able to identify 12 novel PRL-3 inhibitors by means of the virtual screening with docking simulations under the consideration of the effects of ligand solvation in the scoring function. Because the newly identified inhibitors are structurally diverse and reveal a significant potency with IC(50) values ranging from 10 to 50muM, all of them can be considered for further development by structure-activity relationship or de novo design methods. Structural features relevant to the interactions of the newly identified inhibitors with the amino acid residues in the active site and the peripheral binding site of PRL-3 are discussed in detail.
authors: Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea. hspark@sejong.ac.kr
authors: Hwangseo
authors: H
authors: Park
authors: Suk-Kyeong
authors: SK
authors: Jung
authors: Dae Gwin
authors: DG
authors: Jeong
authors: Seong Eon
authors: SE
authors: Ryu
authors: Seung Jun
authors: SJ
authors: Kim
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D017076:Computer-Aided Design; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D008024:Ligands; D017027:Protein Tyrosine Phosphatases