Druggable targets of protein tyrosine phosphatase Family, viz. PTP1B, SHP2, Cdc25, and LMW-PTP: Current scenario on medicinal Attributes, and SAR insights.

Bhavana, Rupali Kohal, Preety Kumari, Ghanshyam Das Gupta, Sant Kumar Verma

Bioorganic chemistry 2024 Mar

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Protein tyrosine phosphatases (PTPs) are the class of dephosphorylation enzymes that catalyze the removal of phosphate groups from tyrosine residues on proteins responsible for various cellular processes. Any disbalance in signal pathways mediated by PTPs leads to various disease conditions like diabetes, obesity, cancers, and autoimmune disorders. Amongst the PTP superfamily, PTP1B, SHP2, Cdc25, and LMW-PTP have been prioritized as druggable targets for developing medicinal agents. PTP1B is an intracellular PTP enzyme that downregulates insulin and leptin signaling pathways and is involved in insulin resistance and glucose homeostasis. SHP2 is involved in the RAS-MAPK pathway and T cell immunity. Cdk-cyclin complex activation occurs by Cdc25-PTPs involved in cell cycle regulation. LMW-PTPs are involved in PDGF/PDGFR, Eph/ephrin, and insulin signaling pathways, resulting in certain diseases like diabetes mellitus, obesity, and cancer. The signaling cascades of PTP1B, SHP2, Cdc25, and LMW-PTPs have been described to rationalize their medicinal importance in the pathophysiology of diabetes, obesity, and cancer. Their binding sites have been explored to overcome the hurdles in discovering target selective molecules with optimum potency. Recent developments in the synthetic molecules bearing heterocyclic moieties against these targets have been explored to gain insight into structural features. The elaborated SAR investigation revealed the effect of substituents on the potency and target selectivity, which can be implicated in the further discovery of newer medicinal agents targeting the druggable members of the PTP superfamily. Copyright © 2024 Elsevier Inc. All rights reserved.

Citation

Bhavana, Rupali Kohal, Preety Kumari, Ghanshyam Das Gupta, Sant Kumar Verma. Druggable targets of protein tyrosine phosphatase Family, viz. PTP1B, SHP2, Cdc25, and LMW-PTP: Current scenario on medicinal Attributes, and SAR insights. Bioorganic chemistry. 2024 Mar;144:107121