ArticleNature chemical biology2014
Targeting the disordered C terminus of PTP1B with an allosteric inhibitor.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 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
211 citing papers in PubMed, 375 citations in OpenAlex.
- A Potent and Selective Quinolone-Based PTPN22 Inhibitor with Improved Immunotherapeutic Activity.Journal of medicinal chemistry · 2026Article
- Uncompetitive Allosteric Inhibition of PTP1B by BP-1-102 Reveals a Potential Dual-Target Strategy toward the PTP1B-STAT3 Oncogenic Axis: Biochemical and Computational Evidence.ACS medicinal chemistry letters · 2026Article
- Phosphorylation tunes strain-specific protein condensation during rotavirus replication organelle assembly.The EMBO journal · 2026Article
- Ganaxolone, an approved therapy for CDKL5-deficiency disorder, is an inhibitor of PTP1B.The Journal of biological chemistry · 2026Article
- Inhibition of protein tyrosine phosphatase PTP1B function ameliorates pathophysiological deficits in Rett Syndrome.bioRxiv : the preprint server for biology · 2026Article
- Structural basis of Fumosorinone-mediated allosteric inhibition of PTP1B for cancer immunotherapy.Communications biology · 2026Article
- Resveratrol Induces Proteasomal Degradation of PTPN1 to Enhance Cisplatin Sensitivity in Epstein-Barr Virus-Associated Malignancies.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Phosphatase Signaling as a Therapeutic Strategy in Schizophrenia.International journal of molecular sciences · 2026Review
- Targeting Protein Tyrosine Phosphatase 1B (PTP1B) to Improve Insulin Sensitivity Using Indole-Fused Glycyrrhetinic Acid Conjugates with Amino Acids.ACS medicinal chemistry letters · 2026Article
- Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.Science advances · 2026Article
- Optimization of Indole- and Pyrazole-fused Glycyrrhetinic Acid Derivatives as Potent PTP1B Inhibitors: In Silico, In Vitro, In Vivo, and Metabolomic Studies.ACS bio & med chem Au · 2026Article
- PTP1B inhibition promotes microglial phagocytosis in Alzheimer's disease models by enhancing SYK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mechanisms, functions and therapeutic targeting of protein tyrosine phosphatases.Nature reviews. Molecular cell biology · 2026Review
- Organoplatinum(II) Type II Immunogenic Cell Death Inducers Target Protein Tyrosine Phosphatase 1B to Drive Immunogenicity.Journal of the American Chemical Society · 2026Article
- Discovery of Novel PTP1B Inhibitors by High-throughput Virtual Screening.Current computer-aided drug design · 2026Article
- False Friends in Fluorescence - Simple HPLC Evaluation of False Positive Fragment Hits in a DiFMUP Assay for Protein Tyrosine Phosphatase 1B.Drug design, development and therapy · 2026Article
- Article
- Uncovering the individual immunotherapeutic roles of PTPN1 and PTPN2 in T cells during dual inhibition.iScience · 2025Article
- Article
- Article
151 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
PTP1B, a validated therapeutic target for diabetes and obesity, has a critical positive role in HER2 signaling in breast tumorigenesis. Efforts to develop therapeutic inhibitors of PTP1B have been frustrated by the chemical properties of the active site. We define a new mechanism of allosteric inhibition that targets the C-terminal, noncatalytic segment of PTP1B. We present what is to our knowledge the first ensemble structure of PTP1B containing this intrinsically disordered segment, within which we identified a binding site for the small-molecule inhibitor MSI-1436. We demonstrate binding to a second site close to the catalytic domain, with cooperative effects between the two sites locking PTP1B in an inactive state. MSI-1436 antagonized HER2 signaling, inhibited tumorigenesis in xenografts and abrogated metastasis in the NDL2 mouse model of breast cancer, validating inhibition of PTP1B as a therapeutic strategy in breast cancer. This new approach to inhibition of PTP1B emphasizes the potential of disordered segments of proteins as specific binding sites for therapeutic small molecules.
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.