Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Protein-tyrosine phosphatase-2 (SHP-2) has become a new target in the study of type 2 diabetes mellitus (T2DM). Currently, there are no marketed drugs targeting SHP-2 to study T2DM caused by insulin resistance. Therefore, this study screened out SHP-2 inhibitors with potential inhibitory activity from 2 million compounds, combined with ADME/T, Lipinski &Veber rules, molecular docking and molecular dynamics simulation. It is understood that the mechanism of action to inhibit the activity of SHP-2 protein by compounds is mainly protein amino acid residues PHE-113, GLU-250, LEU-254, GLN-257, PRO-491, and GLN-495 bind to ligands to produce stable conformation. Finally, a series of in vitro preliminary evaluation experiments were conducted to verify the primary activity of the lead compounds. It provides a meaningful reference for the future study of SHP-2 inhibitors with better efficacy, safety, drug-like, bioavailability and drug resistance.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s11030-025-11344-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Computational insights and activity evaluation of novel SHP-2 inhibitors for targeting type 2 diabetes mellitus.
Mol Divers
September 2025
School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 400054, China.
Protein-tyrosine phosphatase-2 (SHP-2) has become a new target in the study of type 2 diabetes mellitus (T2DM). Currently, there are no marketed drugs targeting SHP-2 to study T2DM caused by insulin resistance. Therefore, this study screened out SHP-2 inhibitors with potential inhibitory activity from 2 million compounds, combined with ADME/T, Lipinski &Veber rules, molecular docking and molecular dynamics simulation.
View Article and Find Full Text PDFHypoxia suppressed the Siglec-5 signaling in TAMs via modulating the balance of SHP2/SYK activation in hepatocellular carcinoma.
Sci Rep
August 2025
The People's Hospital of Xishuangbanna Dai Autonomous Prefecture Medical Laboratory, 4 Gai Lan Nan Road, Jinghong Street, Jinghong City, Xishuangbanna Dai Autonomous Prefecture, 666100, Yunnan Province, China.
Objective: To investigate the effects of Siglec-5 on hepatocellular carcinoma and the mechanism of action. The interactions and expression changes between Siglec-5 and Siglec-14 not only affect immune cell function, but may also influence tumor progression. A deeper understanding of the mechanisms regulating their balance could provide new insights and strategies for hepatocellular carcinoma treatment.
View Article and Find Full Text PDFSHP2 is a multifunctional target in anaplastic thyroid carcinoma: Cell intrinsic and immune-dependent anti-tumor effects.
Biomed Pharmacother
September 2025
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Italy. Electronic address:
Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive malignancy with dismal prognosis. Standard radiotherapy and chemotherapy offer limited efficacy, and emerging treatments, including multi-kinase inhibitors, often result in the development of adaptive drug resistance. Recent studies suggest that targeting SHP2 (PTPN11), a non-receptor tyrosine phosphatase involved in RAS/MAPK signaling, may offer a promising therapeutic strategy for tumors featuring activation of this pathway, including ATC.
View Article and Find Full Text PDFStructure-guided expansion strategy unveils potent allosteric SHP2 inhibitors with synergistic efficacy against AML through MCL-1 co-targeting.
Eur J Med Chem
November 2025
School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address:
SHP2, an oncogenic phosphatase pivotal in RAS-MAPK, PI3K-AKT, and JAK-STAT signaling, represents a compelling therapeutic target in malignancies driven by its hyperactivation. While allosteric inhibitors like SHP099 have overcome historical challenges of orthosteric agents by stabilizing SHP2's autoinhibited conformation, opportunities remain to enhance potency, selectivity, and clinical utility. Here, we report a structure-guided expansion strategy leveraging detailed profiling of the tunnel-shaped allosteric pocket to design next-generation inhibitors.
View Article and Find Full Text PDFProteomic analyses identify targets, pathways, and cellular consequences of oncogenic KRAS signaling.
Sci Signal
July 2025
School of Life Sciences, Technical University of Munich, Freising, Germany.
Mutations that activate the small GTPase KRAS are a frequent genetic alteration in cancer, and drug discovery efforts have led to inhibitors that block KRAS activity. We sought to better understand oncogenic KRAS signaling and the cytostatic effects of drugs that target this system. We performed proteomic analyses to investigate changes in protein abundance and posttranslational modifications in inhibitor-treated human KRAS-mutant pancreatic (KRAS G12C and G12D) and lung cancer (KRAS G12C) cells.
View Article and Find Full Text PDF