Protein Tyrosine Phosphatase (PTP1B): A promising Drug Target Against Life-threatening Ailments

Abstract

Background: Protein tyrosine phosphatases are enzymes which help in the signal transduction in diabetes, obesity, cancer, liver diseases and neurodegenerative diseases. PTP1B is the main member of this enzyme from the protein extract of human placenta. In phosphate inhibitors development, significant progress has been made over the last 10 years. In early-stage clinical trials, few compounds have reached whereas in the later stage trials or registration, yet none have progressed. Many researchers investigate different ways to improve the pharmacological properties of PTP1B inhibitors. Objective: In the present review, authors have summarized various aspects related to the involvement of PTP1B in various types of signal transduction mechanisms and its prominent role in various diseases like cancer, liver diseases and diabetes mellitus. Conclusion: There are still certain challenges for the selection of PTP1B as a drug target. Therefore, continuous future efforts are required to explore this target for the development of PTP inhibitors to treat the prevailing diseases associated with it.

Anti‐obesity effect of plant diterpenes and their derivatives: A review

“…On the other hand, PTP1B serves as a key negative regulator of the tyrosine phosphorylation cascade integral to the leptin and insulin signaling pathway and has been proposed as a therapy to treat type 2 diabetes and obesity. Inhibition of PTP1B may be an attractive target to improve insulin sensitivity in different cell types (Través et al, ) and has potential benefits for the treatment of some diseases, including diabetes, obesity, cancer, liver diseases, and neurodegenerative diseases (Kumar, Rana, Rana, & Bhatia, ). Along this line, a number of diterpenes and their derivatives have been shown to inhibit PTP1B activity.…”

Ophiopogonin‑B targets PTP1B to inhibit the malignant progression of hepatocellular carcinoma by regulating the PI3K/AKT and AMPK signaling pathways

“…Protein tyrosine phosphatase 1B [PTP1B; encoded by protein tyrosine phosphatase non-receptor type 1 (PTPN1)] is an important member in PTP superfamily of proteins. PTPs catalyze phosphate monoesters hydrolysis on tyrosine residues; they are also known to act as signaling molecules to regulate a number of cellular processes, including cell growth, differentiation, mitotic cycle and oncogenic transformation ( 12 ). To date, PTP1B has been reported to be also involved in the development of obesity, diabetes, cancers and cardiovascular diseases ( 13 ).…”

Structural Bases for Hesperetin Derivatives: Inhibition of Protein Tyrosine Phosphatase 1B, Kinetics Mechanism and Molecular Docking Study

“…Recent studies on the pathological mechanism revealed that DM has a close relation to the protein tyrosine phosphatase (PTP) family, which plays a pivotal role in the regulation of insulin function by dephosphorylating the tyrosine residues of proteins [6]. Among the PTP family, PTP1B is a critical member and is in charge of insulin and leptin signaling pathways, and is a negative regulator of the insulin receptor (IR) signal transduction pathway that leads to insulin resistance, which makes this enzyme a promising therapeutic Molecules 2021, 26, 7433 2 of 16 target to manage DM [7,8]. In insulin signaling, PTP1B is known to dephosphorylate the activated insulin receptor and insulin receptor substrates to attenuate the cellular response to insulin binding [7,9].…”

“…Among the PTP family, PTP1B is a critical member and is in charge of insulin and leptin signaling pathways, and is a negative regulator of the insulin receptor (IR) signal transduction pathway that leads to insulin resistance, which makes this enzyme a promising therapeutic Molecules 2021, 26, 7433 2 of 16 target to manage DM [7,8]. In insulin signaling, PTP1B is known to dephosphorylate the activated insulin receptor and insulin receptor substrates to attenuate the cellular response to insulin binding [7,9]. Mice with PTP1B gene knockouts have enhanced insulin sensitivity and low body weight, even when fed a high-fat diet [10].…”

“…For these reasons, PTP1B has become an active therapeutic target for the treatment of type II diabetes. Since PTP1B was discovered more than 25 years ago, it has proven to play a critical role in multiple cellular processes, particularly glucose uptake, body mass regulation, motility, and proliferation [7,11]. Considering the rationale above, PTP1B inhibition may modulate DM, and thus, is an outstanding target for the treatment of this epidemic disease.…”