ArticleJournal of lipid research2016
Human sterol 14α-demethylase as a target for anticancer chemotherapy: towards structure-aided drug design.
Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Cryo-EM reveals an ensemble of cytochrome P450 reductase conformations in solution.Protein science : a publication of the Protein Society · 2026Article
- A bypass gateway from cholesterol to sex steroid biosynthesis circumnavigates CYP17A1.Nature communications · 2025Article
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- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Unique Structural Features Relate to Evolutionary Adaptation of Cytochrome P450 in the Abyssal Zone.International journal of molecular sciences · 2025Article
- A First-in-Class Pyrazole-isoxazole Enhanced Antifungal Activity of Voriconazole: Synergy Studies in an Azole-ResistantJournal of medicinal chemistry · 2024Article
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
- High Starch Induces Hematological Variations, Metabolic Changes, Oxidative Stress, Inflammatory Responses, and Histopathological Lesions in Largemouth Bass (Metabolites · 2024Article
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- Targeting Cytochrome P450 Enzymes in Ovarian Cancers: New Approaches to Tumor-Selective Intervention.Biomedicines · 2023Review
- Revealing substrate-induced structural changes in active site of human CYP51 in the presence of its physiological substrates.Journal of inorganic biochemistry · 2023Article
- Knockout of Nur77 Leads to Amino Acid, Lipid, and Glucose Metabolism Disorders in Zebrafish.Frontiers in endocrinology · 2022Article
- A Yeast-Based Repurposing Approach for the Treatment of Mitochondrial DNA Depletion Syndromes Led to the Identification of Molecules Able to Modulate the dNTP Pool.International journal of molecular sciences · 2021Article
- Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context.Biomedicines · 2021Article
- Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker.ACS infectious diseases · 2021Article
- The antifungal drug isavuconazole inhibits the replication of human cytomegalovirus (HCMV) and acts synergistically with anti-HCMV drugs.Antiviral research · 2021Article
- Concerning P450 Evolution: Structural Analyses Support Bacterial Origin of Sterol 14α-Demethylases.Molecular biology and evolution · 2021Article
- The Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus Replication.Antimicrobial agents and chemotherapy · 2020Article
- A requirement for an active proton delivery network supports a compound I-mediated C-C bond cleavage in CYP51 catalysis.The Journal of biological chemistry · 2020Article
- Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis.FASEB bioAdvances · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Rapidly multiplying cancer cells synthesize greater amounts of cholesterol to build their membranes. Cholesterol-lowering drugs (statins) are currently in clinical trials for anticancer chemotherapy. However, given at higher doses, statins cause serious side effects by inhibiting the formation of other biologically important molecules derived from mevalonate. Sterol 14α-demethylase (CYP51), which acts 10 steps downstream, is potentially a more specific drug target because this portion of the pathway is fully committed to cholesterol production. However, screening a variety of commercial and experimental inhibitors of microbial CYP51 orthologs revealed that most of them (including all clinical antifungals) weakly inhibit human CYP51 activity, even if they display high apparent spectral binding affinity. Only one relatively potent compound, (R)-N-(1-(3,4'-difluorobiphenyl-4-yl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VFV), was identified. VFV has been further tested in cellular experiments and found to decrease proliferation of different cancer cell types. The crystal structures of human CYP51-VFV complexes (2.0 and 2.5 Å) both display a 2:1 inhibitor/enzyme stoichiometry, provide molecular insights regarding a broader substrate profile, faster catalysis, and weaker susceptibility of human CYP51 to inhibition, and outline directions for the development of more potent 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.