ArticleJournal of medicinal chemistry2011
Itraconazole side chain analogues: structure-activity relationship studies for inhibition of endothelial cell proliferation, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, and hedgehog signaling.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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
21 citing papers in PubMed, 43 citations in OpenAlex.
- A Phase II Trial of Perioperative Oral Itraconazole for the Management of Low-Risk Basal Cell Carcinoma.Experimental dermatology · 2026Trial
- Nemacol is a small molecule inhibitor of C. elegans vesicular acetylcholine transporter with anthelmintic potential.Nature communications · 2023Article
- Targeting Angiogenic Factors for the Treatment of Medulloblastoma.Current treatment options in oncology · 2022Review
- Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances.Frontiers in oncology · 2022Review
- Design and Synthesis of Tetrazole- and Pyridine-Containing Itraconazole Analogs as Potent Angiogenesis Inhibitors.ACS medicinal chemistry letters · 2020Article
- Inhibition of hedgehog signaling by stereochemically defined des-triazole itraconazole analogues.Bioorganic & medicinal chemistry letters · 2020Article
- Investigation of the Detailed Internal Structure and Dynamics of Itraconazole by Solid-State NMR Measurements.ACS omega · 2019Article
- Truncated Itraconazole Analogues Exhibiting Potent Anti-Hedgehog Activity and Improved Drug-like Properties.ACS medicinal chemistry letters · 2019Article
- Design of Hedgehog pathway inhibitors for cancer treatment.Medicinal research reviews · 2019Review
- Structure-Activity Relationships for Itraconazole-Based Triazolone Analogues as Hedgehog Pathway Inhibitors.Journal of medicinal chemistry · 2019Article
- Inhibition of the hedgehog pathway for the treatment of cancer using Itraconazole.OncoTargets and therapy · 2019Article
- Itch/β-arrestin2-dependent non-proteolytic ubiquitylation of SuFu controls Hedgehog signalling and medulloblastoma tumorigenesis.Nature communications · 2018Article
- Simultaneous Targeting of NPC1 and VDAC1 by Itraconazole Leads to Synergistic Inhibition of mTOR Signaling and Angiogenesis.ACS chemical biology · 2017Article
- Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety.Molecules (Basel, Switzerland) · 2016Article
- Identification of Small Molecule-binding Proteins in a Native Cellular Environment by Live-cell Photoaffinity Labeling.Journal of visualized experiments : JoVE · 2016Article
- Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic.Journal of medicinal chemistry · 2016Article
- Antifungal drug itraconazole targets VDAC1 to modulate the AMPK/mTOR signaling axis in endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Synthetic Small Molecule Inhibitors of Hh Signaling As Anti-Cancer Chemotherapeutics.Current medicinal chemistry · 2015Review
- Druggable glycolytic requirement for Hedgehog-dependent neuronal and medulloblastoma growth.Cell cycle (Georgetown, Tex.) · 2014Article
- Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation and tumor growth associated with acquired resistance to smoothened antagonists.Cancer cell · 2013Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure-activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole.
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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.