Discovery of novel PRL-3 inhibitors based on the structure-based virtual screening.
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.
Park
Hwangseo
H
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong, Kwangjin-Ku, Seoul 143-747, Republic of Korea. hspark@sejong.ac.kr
Jung
Suk-Kyeong
SK
Jeong
Dae Gwin
DG
Ryu
Seong Eon
SE
Kim
Seung Jun
SJ
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
D000596:Amino Acids; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D008024:Ligands; D017027:Protein Tyrosine Phosphatases