Recent findings of very strong inhibition of some PTPs by zinc ions at concentrations relevant in a cellular environment suggest yet another mechanism of regulation. One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes.

One of the most extensively investigated PTPs is PTP1B (PTPN1). It regulates the insulin and leptin signalling pathway and is implicated in cancer and obesity/diabetes. The development of novel assay conditions to investigate zinc inhibition of PTP1B provides estimates of about 5.6 nM affinity for inhibitory zinc (II) ions.

2024年3月1日 · The current study has employed advanced computational methods to explore the binding and conformational orientation of zinc (II) complexes in the active site of apoenzyme, phosphoenzyme, and TSA 2 of PTP1B. Metal ion modeling was performed for zinc metal center (Zn-OOOO) utilizing a Python based Metal Center Parameter Builder (MCPB.py).

2016年11月15日 · Our results explain the apparent dichotomy of both cations (Zn 2+) and oxyanions such as vanadate inhibiting PTP1B and having insulin-enhancing (“anti-diabetic”) effects and suggest different approaches, namely targeting PTPs in the cell by affecting their physiological modulators and considering a metallodrug approach that builds on the knowled...

已经发现它们是四种重组PTP的有效抑制剂，包括蛋白酪氨酸磷酸酶1B（PTP1B），T细胞蛋白酪氨酸磷酸酶（TCPTP），巨核细胞蛋白酪氨酸磷酸酶2（PTP-MEG2）和Src同源磷酸酶1（ SHP-1），Src同源磷酸酶2（SHP-2）除外。

2012年3月10日 · The present study describes identification of a novel lead molecule ZINC02765569 for inhibition of protein tyrosine phosphatase 1B (PTP1B) enzyme by a high-throughput virtual screening of Zinc database against catalytic domain of PTP1B employing docking algorithm Glide.

2012年9月11日 · In the present study, we identified novel classes of PTP1B inhibitors by means of a structure-based drug design protocol involving virtual screening with docking. 523,366 molecules from ZINC database have been screened and based on DOCK grid scores five new inhibitors were identified.

2019年3月22日 · Although protein tyrosine phosphatases (PTPs) do not contain any metals, their activities can be inhibited by some metal complexes. Here we investigated the inhibition of two zinc complexes with Schiff base ligands against PTPs …

Vanadium and zinc metal coordinated complexes have insulin-enhancing activities, and while vanadium compounds inhibit PTP1B, little is known on the mode of action of zinc compounds. In this study we developed an automated PTP1B inhibition assay that allows for a rapid assessment of the PTP1B inhibition strength of candidate compounds.

PTP1B is regulated by both cell redox and zinc status [14]. Oxidation of a cysteine to sulfenylamide in the PTP1B catalytic domain inhibits the activity of the enzyme [54], [55], while zinc per se inhibits PTP1B [56] which would lead to its activation in conditions of zinc deficits.