ArticleBioorganic & medicinal chemistry2016
Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP).
Article in Bioorganic & medicinal chemistry, 2016. 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, 71 citations in OpenAlex.
- Molecular mechanism of CtBP1-S/BARS-driven membrane fission and its cellular control by metabolic ligands.Science advances · 2026Article
- Combined inhibition of NAD synthesis and C-terminal binding protein cooperatively induces cell death and inhibits growth of high grade serous ovarian carcinoma.Scientific reports · 2025Article
- The specificity of CTBP dehydrogenase inhibitors MTOB and 4-Cl-HIPP.microPublication biology · 2025Article
- A new method for network bioinformatics identifies novel drug targets for mucinous ovarian carcinoma.NAR genomics and bioinformatics · 2024Article
- Review
- Identification and characterization of a new potent inhibitor targeting CtBP1/BARS in melanoma cells.Journal of experimental & clinical cancer research : CR · 2024Article
- Cleavage of the pseudoprotease iRhom2 by the signal peptidase complex reveals an ER-to-nucleus signaling pathway.Molecular cell · 2024Article
- Merging cultures and disciplines to create a drug discovery ecosystem at Virginia commonwealth university: Medicinal chemistry, structural biology, molecular and behavioral pharmacology and computational chemistry.SLAS discovery : advancing life sciences R & D · 2023Review
- Elevation of hsa-miR-7-5p level mediated by CtBP1-p300-AP1 complex targets ATXN1 to trigger NF-κB-dependent inflammation response.Journal of molecular medicine (Berlin, Germany) · 2023Article
- Transcriptomics and Metabolomics Integration Reveals Redox-Dependent Metabolic Rewiring in Breast Cancer Cells.Cancers · 2021Article
- The transrepression and transactivation roles of CtBPs in the pathogenesis of different diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Presence of Bromotyrosine Alkaloids in Marine Sponges Is Independent of Metabolomic and Microbiome Architectures.mSystems · 2021Article
- Epstein-Barr virus nuclear antigen 3C (EBNA3C) interacts with the metabolism sensing C-terminal binding protein (CtBP) repressor to upregulate host genes.PLoS pathogens · 2021Article
- CtBP determines ovarian cancer cell fate through repression of death receptors.Cell death & disease · 2020Article
- CtBP-a targetable dependency for tumor-initiating cell activity and metastasis in pancreatic adenocarcinoma.Oncogenesis · 2019Article
- Epigenetic re-wiring of breast cancer by pharmacological targeting of C-terminal binding protein.Cell death & disease · 2019Article
- Active-Site Tryptophan, the Target of Antineoplastic C-Terminal Binding Protein Inhibitors, Mediates Inhibitor Disruption of CtBP Oligomerization and Transcription Coregulatory Activities.Molecular pharmacology · 2019Article
- An intestinal stem cell niche inOncotarget · 2018Article
- CPP-E1A fusion peptides inhibit CtBP-mediated transcriptional repression.Molecular oncology · 2018Article
- Transforming activity and therapeutic targeting of C-terminal-binding protein 2 in Apc-mutated neoplasia.Oncogene · 2017Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD(+) as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50=0.24μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50=0.18μM) and 3-chloro- (IC50=0.17μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.
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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.