ArticleACS omega2018
The Allosteric Site on SHP2's Protein Tyrosine Phosphatase Domain is Targetable with Druglike Small Molecules.
Article in ACS omega, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 40 citations in OpenAlex.
- Deciphering SHP-2 conformational switching via elastic network models and transfer entropy analysis.Journal of molecular modeling · 2026Article
- High-throughput biochemical phenotyping of SHP2 variants reveals the molecular basis of diseases and allosteric drug inhibition.bioRxiv : the preprint server for biology · 2026Article
- Mapping the SHP2 Allosteric Pocket With Target-Biased Covalent Fragments.Chembiochem : a European journal of chemical biology · 2026Article
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Applications of Bridgehead Heterocycles in Drug Design and Medicinal Chemistry.Topics in current chemistry (Cham) · 2025Review
- Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?Journal of medicinal chemistry · 2025Review
- Emerging regulatory mechanisms and functions of biomolecular condensates: implications for therapeutic targets.Signal transduction and targeted therapy · 2025Review
- Targeting Nonconserved and Pathogenic Cysteines of Protein Tyrosine Phosphatases with Small Molecules.Methods in molecular biology (Clifton, N.J.) · 2024Article
- High-Throughput Discovery and Characterization of Covalent Inhibitors for Protein Tyrosine Phosphatases.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Destabilization of the SHP2 and SHP1 protein tyrosine phosphatase domains by a non-conserved "backdoor" cysteine.Biochemistry and biophysics reports · 2022Article
- Inhibition of SHP2 and SHP1 Protein Tyrosine Phosphatase Activity by Chemically Induced Dimerization.ACS omega · 2022Article
- Strategies to overcome drug resistance using SHP2 inhibitors.Acta pharmaceutica Sinica. B · 2021Review
- Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies.Acta pharmaceutica Sinica. B · 2021Review
- Targeting a Pathogenic Cysteine Mutation: Discovery of a Specific Inhibitor of Y279C SHP2.Biochemistry · 2020Article
- Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020Review
- Design, Synthesis, and In Vitro Activity of Pyrazine Compounds.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Difficulties in developing active-site-directed protein tyrosine phosphatase (PTP) inhibitors have led to the perception that PTPs are "undruggable", highlighting the need for new means to target pharmaceutically important PTPs allosterically. Recently, we characterized an allosteric-inhibition site on the PTP domain of Src-homology-2-domain-containing PTP 2 (SHP2), a key anticancer drug target. The central feature of SHP2's allosteric site is a nonconserved cysteine residue (C333) that can potentially be labeled with electrophilic compounds for selective SHP2 inhibition. Here, we describe the first directed discovery effort for C333-targeted allosteric SHP2 inhibitors. By screening a previously reported library of reversible, covalent inhibitors, we identified a lead compound, which was modified to yield an irreversible inhibitor (
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.