ArticleJournal of medicinal chemistry2014
Therapeutic potential of targeting the oncogenic SHP2 phosphatase.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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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.
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Who cites it
55 citing papers in PubMed, 131 citations in OpenAlex.
- A Potent and Selective Quinolone-Based PTPN22 Inhibitor with Improved Immunotherapeutic Activity.Journal of medicinal chemistry · 2026Article
- Allosteric PROTACs: Expanding the Horizon of Targeted Protein Degradation.Journal of the American Chemical Society · 2026Review
- Regulation and activity of the phosphatase SHP2: SH2 domains, dephosphorylation activity, and beyond.Biochemical Society transactions · 2026Review
- Development of a Peptide Inhibitor Targeting the C-SH2 Domain of the SHP2 Phosphatase.Chembiochem : a European journal of chemical biology · 2025Article
- Discovery and Evaluation of Active Site-Directed, Potent, and Selective Sulfophenyl Acetic Amide-Based Inhibitors for the Laforin Phosphatase.Journal of medicinal chemistry · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Development of Novel Phosphonodifluoromethyl-Containing Phosphotyrosine Mimetics and a First-In-Class, Potent, Selective, and Bioavailable Inhibitor of Human CDC14 Phosphatases.Journal of medicinal chemistry · 2024Article
- Targeting SHP2 with an Active Site Inhibitor Blocks Signaling and Breast Cancer Cell Phenotypes.ACS bio & med chem Au · 2023Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Toward a Treatment of Cancer: Design and In Vitro/In Vivo Evaluation of Uncharged Pyrazoline Derivatives as a Series of Novel SHP2 Inhibitors.International journal of molecular sciences · 2022Article
- Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors.RSC medicinal chemistry · 2022Review
- The Q61H mutation decouples KRAS from upstream regulation and renders cancer cells resistant to SHP2 inhibitors.Nature communications · 2021Article
- Functional interrogation and therapeutic targeting of protein tyrosine phosphatases.Biochemical Society transactions · 2021Review
- Discovery of Orally Bioavailable Purine-Based Inhibitors of the Low-Molecular-Weight Protein Tyrosine Phosphatase.Journal of medicinal chemistry · 2021Article
- SHP2 is a multifunctional therapeutic target in drug resistant metastatic breast cancer.Oncogene · 2020Article
- Novel Small-Molecule Inhibitor for the Oncogenic Tyrosine Phosphatase SHP2 with Anti-Breast Cancer Cell Effects.ACS omega · 2020Article
- Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The Src homology 2 domain containing protein tyrosine phosphatase-2 (SHP2) is an oncogenic phosphatase associated with various kinds of leukemia and solid tumors. Thus, there is substantial interest in developing SHP2 inhibitors as potential anticancer and antileukemia agents. Using a structure-guided and fragment-based library approach, we identified a novel hydroxyindole carboxylic acid-based SHP2 inhibitor 11a-1, with an IC50 value of 200 nM and greater than 5-fold selectivity against 20 mammalian PTPs. Structural and modeling studies reveal that the hydroxyindole carboxylic acid anchors the inhibitor to the SHP2 active site, while interactions of the oxalamide linker and the phenylthiophene tail with residues in the β5-β6 loop contribute to 11a-1's binding potency and selectivity. Evidence suggests that 11a-1 specifically attenuates the SHP2-dependent signaling inside the cell. Moreover, 11a-1 blocks growth factor mediated Erk1/2 and Akt activation and exhibits excellent antiproliferative activity in lung cancer and breast cancer as well as leukemia cell lines.
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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.