ArticleBioorganic & medicinal chemistry letters2011
Small molecule inhibitors of SHP2 tyrosine phosphatase discovered by virtual screening.
Article in Bioorganic & medicinal chemistry letters, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Cancer-Causing Mutations Alter the Interplay Between Loop Dynamics and Catalysis in the Protein Tyrosine Phosphatases SHP-1 and SHP-2.bioRxiv : the preprint server for biology · 2026Article
- Diabetes-compound Relationship Identification based on Complex-valued Flexible Neural Tree and Negative Sample Selection Algorithm.Current computer-aided drug design · 2025Article
- Development and validation of machine learning models for the prediction of SH-2 containing protein tyrosine phosphatase 2 inhibitors.Molecular diversity · 2024Article
- SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47/SIRPα axis.The Journal of clinical investigation · 2023Article
- Structural insights into the pSer/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling.Nature communications · 2022Article
- Novel Small-Molecule Inhibitor for the Oncogenic Tyrosine Phosphatase SHP2 with Anti-Breast Cancer Cell Effects.ACS omega · 2020Article
- A specific amino acid context in EGFR and HER2 phosphorylation sites enables selective binding to the active site of Src homology phosphatase 2 (SHP2).The Journal of biological chemistry · 2020Article
- Synthesis of small peptide compounds, molecular docking, and inhibitory activity evaluation against phosphatases PTP1B and SHP2.Drug design, development and therapy · 2018Article
- A tyrosine phosphatase SHP2 gain-of-function mutation enhances malignancy of breast carcinoma.Oncotarget · 2016Article
- DOCK 6: Impact of new features and current docking performance.Journal of computational chemistry · 2015Article
- Therapeutic potential of targeting the oncogenic SHP2 phosphatase.Journal of medicinal chemistry · 2014Article
- Src homology phosphotyrosyl phosphatase-2 expression is an independent negative prognostic factor in human breast cancer.Histopathology · 2013Article
- Small molecule tools for functional interrogation of protein tyrosine phosphatases.The FEBS journal · 2013Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
SHP2, encoded by PTPN11, is a non-receptor protein tyrosine phosphatase (PTP) containing two tandem Src homology-2 (SH2) domains. It is expressed ubiquitously and plays critical roles in growth factor mediated processes, primarily by promoting the activation of the RAS/ERK signaling pathway. Genetic and biochemical studies have identified SHP2 as the first bona fide oncoprotein in the PTP superfamily, and a promising target for anti-cancer and anti-leukemia therapy. Here, we report a structure-based approach to identify SHP2 inhibitors with a novel scaffold. Through sequential virtual screenings and in vitro inhibition assays, a reversible competitive SHP2 inhibitor (C21) was identified. C21 is structurally distinct from all known SHP2 inhibitors. Combining molecular dynamics simulation and binding free energy calculation, a most likely binding mode of C21 with SHP2 is proposed, and further validated by site-directed mutagenesis and structure-activity relationship studies. This binding mode is consistent with the observed potency and specificity of C21, and reveals the molecular determinants for further optimization based on the new scaffold.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.