ArticlePLoS computational biology2015
Novel inhibitors induce large conformational changes of GAB1 pleckstrin homology domain and kill breast cancer cells.
Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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
14 citing papers in PubMed, 29 citations in OpenAlex.
- Decoding Protein-Membrane Binding Interfaces from Surface-Fingerprint-Based Geometric Deep Learning and Molecular Dynamics Simulations.Journal of chemical information and modeling · 2026Article
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Dysregulated Gab1 signalling in triple negative breast cancer.Cell communication and signaling : CCS · 2024Article
- The Role of GAB1 in Cancer.Cancers · 2023Review
- DREAMM: a web-based server for drugging protein-membrane interfaces as a novel workflow for targeted drug design.Bioinformatics (Oxford, England) · 2022Article
- Predicting protein-membrane interfaces of peripheral membrane proteins using ensemble machine learning.Briefings in bioinformatics · 2022Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia.Blood · 2021Article
- Role of EGF Receptor Regulatory Networks in the Host Response to Viral Infections.Frontiers in cellular and infection microbiology · 2021Review
- In silico discovery and biological validation of ligands of FAD synthase, a promising new antimicrobial target.PLoS computational biology · 2020Article
- Elevated expression of Gab1 promotes breast cancer metastasis by dissociating the PAR complex.Journal of experimental & clinical cancer research : CR · 2019Article
- Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells.Oncology research · 2018Article
- Profiling the effects of short time-course cold ischemia on tumor protein phosphorylation using a Bayesian approach.Biometrics · 2018Article
- Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma.Cell research · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The Grb2-associated binding protein 1 (GAB1) integrates signals from different signaling pathways and is over-expressed in many cancers, therefore representing a new therapeutic target. In the present study, we aim to target the pleckstrin homology (PH) domain of GAB1 for cancer treatment. Using homology models we derived, high-throughput virtual screening of five million compounds resulted in five hits which exhibited strong binding affinities to GAB1 PH domain. Our prediction of ligand binding affinities is also in agreement with the experimental KD values. Furthermore, molecular dynamics studies showed that GAB1 PH domain underwent large conformational changes upon ligand binding. Moreover, these hits inhibited the phosphorylation of GAB1 and demonstrated potent, tumor-specific cytotoxicity against MDA-MB-231 and T47D breast cancer cell lines. This effort represents the discovery of first-in-class GAB1 PH domain inhibitors with potential for targeted breast cancer therapy and provides novel insights into structure-based approaches to targeting this protein.
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.