title: Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions.
abstract: Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.
authors.affiliation: Department of Biomedical Chemistry and Nanotechnology Research Center, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Rallabandi Harikrishna
authors.initials: RH
authors.lastname: Reddy
authors.affiliation: Department of Biomedical Chemistry and Nanotechnology Research Center, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Hackyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biomedical Chemistry and Nanotechnology Research Center, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Seungbin
authors.initials: S
authors.lastname: Cha
authors.affiliation: School of Energy Systems Engineering, Chungang University, Seoul 06974, Republic of Korea.
authors.forename: Bongsoo
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Biomedical Chemistry and Nanotechnology Research Center, Konkuk University, Chungju 27478, Republic of Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D020134:Catalytic Domain; D003920:Diabetes Mellitus / Q000188:drug therapy; D004194:Disease; D016503:Drug Delivery Systems; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D010744:Phosphoric Monoester Hydrolases / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology*; D010770:Phosphotransferases / Q000502:physiology; D011487:Protein Conformation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000187:drug effects / Q000502:physiology; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000145:classification / Q000187:drug effects* / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases
keywords: Allosteric targeting; cancers; diabetes; drug designing; molecular docking; protein tyrosine phosphatases