ArticleThe Journal of biological chemistry2014
Changes in signal transducer and activator of transcription 3 (STAT3) dynamics induced by complexation with pharmacological inhibitors of Src homology 2 (SH2) domain dimerization.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 47 citations in OpenAlex.
- Unraveling Stereochemical Structure-Activity Relationships of Sesquiterpene Lactones for Inhibitory Effects on STAT3 Activation.Biomolecules & therapeutics · 2024Article
- Quantitative Hydrogen-Deuterium Exchange Mass Spectrometry for Simultaneous Structural Characterization and Affinity Indexing of Single Target Drug Candidate Libraries.Analytical chemistry · 2024Article
- Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.Translational oncology · 2024Review
- Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.World journal of gastrointestinal oncology · 2024Article
- An Isoxazoloquinone Derivative Inhibits Tumor Growth by Targeting STAT3 and Triggering Its Ubiquitin-Dependent Degradation.Cancers · 2023Article
- Online Fully Automated System for Hydrogen/Deuterium-Exchange Mass Spectrometry with Millisecond Time Resolution.Analytical chemistry · 2023Article
- The complementary roles of STAT3 and STAT1 in cancer biology: insights into tumor pathogenesis and therapeutic strategies.Frontiers in immunology · 2023Review
- Proteomic Approaches to Study SARS-CoV-2 Biology and COVID-19 Pathology.Journal of proteome research · 2021Article
- STAT3 and its targeting inhibitors in osteosarcoma.Cell proliferation · 2021Review
- Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution.Pharmacological reviews · 2020Review
- Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors.Oncology letters · 2020Review
- Suppression of STAT3 Phosphorylation and RelA/p65 Acetylation Mediated by MicroRNA134 Plays a Pivotal Role in the Apoptotic Effect of Lambertianic Acid.International journal of molecular sciences · 2019Article
- BP‑1‑102 exerts an antitumor effect on the AGS human gastric cancer cell line through modulating the STAT3 and MAPK signaling pathways.Molecular medicine reports · 2019Article
- Sonic hedgehog pathway activation is associated with cetuximab resistance and EPHB3 receptor induction in colorectal cancer.Theranostics · 2019Article
- The role of STAT3 in leading the crosstalk between human cancers and the immune system.Cancer letters · 2018Review
- Article
- Conformational Dynamics and Allostery in Pyruvate Kinase.The Journal of biological chemistry · 2016Article
- Allosteric Communication across STAT3 Domains Associated with STAT3 Function and Disease-Causing Mutation.Journal of molecular biology · 2016Article
- Localizing Carbohydrate Binding Sites in Proteins Using Hydrogen/Deuterium Exchange Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2016Article
- Hyperphosphorylation of intrinsically disordered tau protein induces an amyloidogenic shift in its conformational ensemble.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The activity of the transcription factor signal transducer and activator of transcription 3 (STAT3) is dysregulated in a number of hematological and solid malignancies. Development of pharmacological STAT3 Src homology 2 (SH2) domain interaction inhibitors holds great promise for cancer therapy, and a novel class of salicylic acid-based STAT3 dimerization inhibitors that includes orally bioavailable drug candidates has been recently developed. The compounds SF-1-066 and BP-1-102 are predicted to bind to the STAT3 SH2 domain. However, given the highly unstructured and dynamic nature of the SH2 domain, experimental confirmation of this prediction was elusive. We have interrogated the protein-ligand interaction of STAT3 with these small molecule inhibitors by means of time-resolved electrospray ionization hydrogen-deuterium exchange mass spectrometry. Analysis of site-specific evolution of deuterium uptake induced by the complexation of STAT3 with SF-1-066 or BP-1-102 under physiological conditions enabled the mapping of the in silico predicted inhibitor binding site to the STAT3 SH2 domain. The binding of both inhibitors to the SH2 domain resulted in significant local decreases in dynamics, consistent with solvent exclusion at the inhibitor binding site and increased rigidity of the inhibitor-complexed SH2 domain. Interestingly, inhibitor binding induced hot spots of allosteric perturbations outside of the SH2 domain, manifesting mainly as increased deuterium uptake, in regions of STAT3 important for DNA binding and nuclear localization.
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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.