ArticleJournal of medicinal chemistry2021
Targeting Oncogenic Src Homology 2 Domain-Containing Phosphatase 2 (SHP2) by Inhibiting Its Protein-Protein Interactions.
Article in Journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- DeepPath: overcoming data scarcity for protein transition pathway prediction using physics-based deep learning.Chemical science · 2026Article
- Decoding C‑SH2 Domain/Peptide Interactions in SH2 Domain-Containing Tyrosine Phosphatase 2: A Molecular Framework for Rational Inhibitor Design.ACS omega · 2026Article
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Genotype-phenotype correlations with autism spectrum disorder-related traits in noonan syndrome and noonan syndrome with multiple lentigines: a cross-sectional study.Molecular autism · 2025Article
- Update on Structure and Function of SH2 Domains: Mechanisms and Emerging Targeting Strategies.International journal of molecular sciences · 2025Review
- Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase.Chembiochem : a European journal of chemical biology · 2025Article
- PTPN11 in cartilage development, adult homeostasis, and diseases.Bone research · 2025Review
- Targeting SHP2 with Natural Products: Exploring Saponin-Based Allosteric Inhibitors and Their Therapeutic Potential.Current issues in molecular biology · 2025Review
- pH-Responsive Peptide Nanoparticles Deliver Macromolecules to Cells via Endosomal Membrane Nanoporation.ACS nano · 2024Article
- Discovery of Novel Allosteric SHP2 Inhibitor Using Pharmacophore-Based Virtual Screening, Molecular Docking, Molecular Dynamics Simulation, and Principal Component Analysis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor.Molecular medicine (Cambridge, Mass.) · 2024Article
- Novel therapeutic perspectives in Noonan syndrome and RASopathies.European journal of pediatrics · 2024Review
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- SH2db, an information system for the SH2 domain.Nucleic acids research · 2023Article
- In silico mutagenesis-based designing of oncogenic SHP2 peptide to inhibit cancer progression.Scientific reports · 2023Article
- Rational combination of SHP2 and mTOR inhibition for the treatment of hepatocellular carcinoma.Molecular oncology · 2023Article
- Computational Evaluation of Peptide-Protein Binding Affinities: Application of Potential of Mean Force Calculations to SH2 Domains.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- SH2 Domains: Folding, Binding and Therapeutical Approaches.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We developed a new class of inhibitors of protein-protein interactions of the SHP2 phosphatase, which is pivotal in cell signaling and represents a central target in the therapy of cancer and rare diseases. Currently available SHP2 inhibitors target the catalytic site or an allosteric pocket but lack specificity or are ineffective for disease-associated SHP2 mutants. Considering that pathogenic lesions cause signaling hyperactivation due to increased levels of SHP2 association with cognate proteins, we developed peptide-based molecules with nanomolar affinity for the N-terminal Src homology domain of SHP2, good selectivity, stability to degradation, and an affinity for pathogenic variants of SHP2 that is 2-20 times higher than for the wild-type protein. The best peptide reverted the effects of a pathogenic variant (D61G) in zebrafish embryos. Our results provide a novel route for SHP2-targeted therapies and a tool for investigating the role of protein-protein interactions in the function of SHP2.
Indexed as
Identifiers
What OpenQuestion holds
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.