ArticleJournal of medicinal chemistry2016
Iminoguanidines as Allosteric Inhibitors of the Iron-Regulated Heme Oxygenase (HemO) of Pseudomonas aeruginosa.
Article in Journal of medicinal chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Biological and clinical significance of iron inJournal of bacteriology · 2026Review
- Porphyrin pathways as targets for combating antimicrobial resistance: virulence and therapeutic opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Enhancing SILCS-MC via GPU Acceleration and Ligand Conformational Optimization with Genetic and Parallel Tempering Algorithms.The journal of physical chemistry. B · 2024Article
- Site Identification by Ligand Competitive Saturation-Biologics Approach for Structure-Based Protein Charge Prediction.Molecular pharmaceutics · 2023Article
- In silico identification of a βProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Rapid and accurate estimation of protein-ligand relative binding affinities using site-identification by ligand competitive saturation.Chemical science · 2021Article
- Small Molecule Inhibitors of the Bacterioferritin (BfrB)-Ferredoxin (Bfd) Complex Kill Biofilm-EmbeddedACS infectious diseases · 2021Article
- Recombinant Production of Biliverdin IXβ and δ Isomers in the T7 Promoter CompatibleFrontiers in microbiology · 2021Article
- Extracellular haem utilization by the opportunistic pathogen Pseudomonas aeruginosa and its role in virulence and pathogenesis.Advances in microbial physiology · 2021Article
- Immune Modulation by Inhibitors of the HO System.International journal of molecular sciences · 2020Review
- Assessing hERG1 Blockade from Bayesian Machine-Learning-Optimized Site Identification by Ligand Competitive Saturation Simulations.Journal of chemical information and modeling · 2020Article
- Metallotherapeutics development in the age of iron-clad bacteria.Metallomics : integrated biometal science · 2020Review
- Mobilization of Iron Stored in Bacterioferritin Is Required for Metabolic Homeostasis inPathogens (Basel, Switzerland) · 2020Article
- Identification and characterization of fragment binding sites for allosteric ligand design using the site identification by ligand competitive saturation hotspots approach (SILCS-Hotspots).Biochimica et biophysica acta. General subjects · 2020Article
- Article
- Emerging Opportunities To Manipulate Metal Trafficking for Therapeutic Benefit.Inorganic chemistry · 2019Review
- Heme uptake and utilization by hypervirulent Acinetobacter baumannii LAC-4 is dependent on a canonical heme oxygenase (abHemO).Archives of biochemistry and biophysics · 2019Article
- Optimization and Evaluation of Site-Identification by Ligand Competitive Saturation (SILCS) as a Tool for Target-Based Ligand Optimization.Journal of chemical information and modeling · 2019Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
New therapeutic targets are required to combat multidrug resistant infections, such as the iron-regulated heme oxygenase (HemO) of Pseudomonas aeruginosa, due to links between iron and virulence and dependence on heme as an iron source during infection. Herein we report the synthesis and activity of a series of iminoguanidine-based inhibitors of HemO. Compound 23 showed a binding affinity of 5.7 μM and an MIC50 of 52.3 μg/mL against P. aeruginosa PAO1. An in cellulo activity assay was developed by coupling HemO activity to a biliverdin-IXα-dependent infrared fluorescent protein, in which compound 23 showed an EC50 of 11.3 μM. The compounds showed increased activity against clinical isolates of P. aeruginosa, further confirming the target pathway. This class of inhibitors acts by binding to an allosteric site; the novel binding site is proposed in silico and supported by saturation transfer difference (STD) NMR as well as by hydrogen exchange mass spectrometry (HXMS).
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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.