title: Rational design of selective organoruthenium inhibitors of protein tyrosine phosphatase 1B.
abstract: Protein tyrosine phosphatases (PTPs) belong to a large family of important regulatory enzymes involved in vital mammalian signaling pathways. Selective inhibitors of PTPs are highly valuable from a therapeutic standpoint given their association with various pathological conditions. One such target is PTP-1B which has previously been linked to diabetes and cancer. However, developing a selective inhibitor against PTP-1B has proven to be daunting because the enzyme shares a high degree of structural homology with TC-PTP, an essential PTP involved in modulating immune functions. To address this challenge, a series of organoruthenium complexes was developed to bind at the PTP substrate-binding site while simultaneously target the peripheral structural space. By capitalizing on the potential difference in the structural environment proximal to the active site between different PTPs, selectivity toward PTP-1B over TC-PTP was improved, paving the way for organoruthenium complexes as selective PTP-1B metalloinhibitors.
authors.affiliation: Department of Chemistry, National University of Singapore , 3 Science Drive 3, Singapore 117543.
authors.forename: Jun Xiang
authors.initials: JX
authors.lastname: Ong
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Yap
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D012428:Ruthenium; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1