ArticleJournal of molecular medicine (Berlin, Germany)2009
Small-molecule costimulatory blockade: organic dye inhibitors of the CD40-CD154 interaction.
Article in Journal of molecular medicine (Berlin, Germany), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 37 citations in OpenAlex.
- Small-molecule inhibitors of the CD40-CD40L costimulatory interaction are effective in pancreatic islet transplantation and prevention of type 1 diabetes models.Frontiers in immunology · 2024Article
- Small molecules targeting protein-protein interactions for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- Small-Molecule Inhibitors of the Coronavirus Spike: ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2.ACS infectious diseases · 2021Article
- Recent advances in the development of protein-protein interactions modulators: mechanisms and clinical trials.Signal transduction and targeted therapy · 2020Review
- Methylene Blue Inhibits the SARS-CoV-2 Spike-ACE2 Protein-Protein Interaction-a Mechanism that can Contribute to its Antiviral Activity Against COVID-19.Frontiers in pharmacology · 2020Article
- A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.Journal of neuroimmunology · 2019Article
- Design, Synthesis, and Evaluation of Novel Immunomodulatory Small Molecules Targeting the CD40⁻CD154 Costimulatory Protein-Protein Interaction.Molecules (Basel, Switzerland) · 2018Article
- Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.Current topics in medicinal chemistry · 2018Review
- Small-Molecule Inhibitors of the CD40-CD40L Costimulatory Protein-Protein Interaction.Journal of medicinal chemistry · 2017Article
- Targeted disruption of Cd40 in a genetically hypertensive rat model attenuates renal fibrosis and proteinuria, independent of blood pressure.Kidney international · 2017Article
- Comparative proteomics of a model MCF10A-KRasG12V cell line reveals a distinct molecular signature of the KRasG12V cell surface.Oncotarget · 2016Article
- TNF superfamily protein-protein interactions: feasibility of small- molecule modulation.Current drug targets · 2015Review
- A CD40-targeted peptide controls and reverses type 1 diabetes in NOD mice.Diabetologia · 2014Article
- Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction.British journal of pharmacology · 2014Article
- Effects of representative glucocorticoids on TNFα- and CD40L-induced NF-κB activation in sensor cells.Steroids · 2014Article
- The promiscuous protein binding ability of erythrosine B studied by metachromasy (metachromasia).Journal of molecular recognition : JMR · 2013Article
- Advances in targeting cell surface signalling molecules for immune modulation.Nature reviews. Drug discovery · 2013Review
- T cells interact with T cells via CD40-CD154 to promote autoimmunity in type 1 diabetes.European journal of immunology · 2012Article
- Article
- Small molecule inhibition of the TNF family cytokine CD40 ligand through a subunit fracture mechanism.ACS chemical biology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Costimulatory blockade is one of the most promising therapeutic targets in autoimmune diseases as well as in transplant recipients, and inhibition of the cluster of differentiation (CD)40-CD154 interaction, which is required for T cell activation and development of an effective immune response, is particularly promising in islet transplant recipients. Here, we report the ability of several small-molecule organic dyes to concentration dependently inhibit this interaction with IC(50) values in the low-micromolar range. They were found to be considerably more active in inhibiting this interaction than the tumor necrosis factor (TNF)-R1-TNF-alpha or B cell-activating factor (BAFF)-R-BAFF interaction, which are members of the same family. They specifically inhibited CD154-induced cell responses in human B cells as well as in THP-1 myeloid cells, which can serve as surrogate dendritic cells, at concentrations well below their cytotoxic concentrations determined in the same cells. Flow cytometry experiments confirmed their ability to inhibit the CD154-induced, but not the Staphylococcus aureus Cowan I- or phorbol 12-myristate 13-acetate-induced increase in the surface expression of CD54, CD40, and major histocompatibility complex class II. Accordingly, these compounds can be useful not only for experimental investigations involving the inhibition of the CD40-CD154 costimulatory interaction but can also provide important structure-activity relationship information and can serve as the starting point of a targeted drug discovery program.
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.