ArticlePloS one2012
A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Navigating heme pathways: the breach of heme oxygenase and hemin in breast cancer.Molecular and cellular biochemistry · 2025Review
- Identification of Heme Oxygenase-1 as a Putative DNA-Binding Protein.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Discovery of Novel Acetamide-Based Heme Oxygenase-1 Inhibitors with PotentJournal of medicinal chemistry · 2021Article
- Combination of Heme Oxygenase-1 Inhibition and Sigma Receptor Modulation for Anticancer Activity.Molecules (Basel, Switzerland) · 2021Article
- East to West not North-West: Structure-Based Mechanistic Resolution of 8-Hydroxyl Replacement and Resulting Effects on the Activities of Imidazole-Based Heme Oxygenase-1 Inhibitors.The protein journal · 2021Article
- New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2020Article
- Synthetically Lethal Interactions of Heme Oxygenase-1 and Fumarate Hydratase Genes.Biomolecules · 2020Article
- Heme-Dependent ER Stress Apoptosis: A Mechanism for the Selective Toxicity of the Dihydroartemisinin, NSC735847, in Colorectal Cancer Cells.Frontiers in oncology · 2020Article
- Recent Advances in the Understanding of the Reaction Chemistries of the Heme Catabolizing Enzymes HO and BVR Based on High Resolution Protein Structures.Current medicinal chemistry · 2020Review
- Heme oxygenase inhibition in cancers: possible tools and targets.Contemporary oncology (Poznan, Poland) · 2018Review
- Role of Gasotransmitters in Oxidative Stresses, Neuroinflammation, and Neuronal Repair.BioMed research international · 2017Review
- Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds.Journal of the Royal Society, Interface · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC(50) = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50) = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.
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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.