ArticleJournal of medicinal chemistry2019
Molecular Mechanism of Inhibition of Acid Ceramidase by Carmofur.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The trial behind it
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Who cites it
37 citing papers in PubMed.
- Lipid tail length dictates membrane disruption by carmofur analogs and reveals noncanonical modes of action.RSC advances · 2026Article
- Fluorogenic Tissue-Based Assessment of Acid Ceramidase Activity.Bio-protocol · 2026Article
- A multifunctional 5-fluorouracil prodrug: synthesis, biological evaluation, and antitumor mechanism investigation.Molecular diversity · 2026Article
- An innovative machine learning-based QSAR approach for prediction and structural analysis of novel/repurposed acid ceramidase (ASAH1) inhibitors for glioblastoma therapy.Molecular diversity · 2026Article
- Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease.Nature cell biology · 2026Article
- A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways.Biomolecules · 2025Review
- Drug Resistance: The Role of Sphingolipid Metabolism.International journal of molecular sciences · 2025Review
- MCL restrained ROS/AKT/ASAH1 pathway to therapy tamoxifen resistance breast cancer by stabilizing NRF2.Cell proliferation · 2024Article
- Beware ofMolecules (Basel, Switzerland) · 2024Article
- The role of ceranib-2 and its nanoform on the decrease of telomerase levels in human non-small cell cancer.Molecular biology reports · 2024Article
- ASAH1 facilitates TNBC by DUSP5 suppression-driven activation of MAP kinase pathway and represents a therapeutic vulnerability.Cell death & disease · 2024Article
- The role of sphingolipid rheostat in the adult-type diffuse glioma pathogenesis.Frontiers in cell and developmental biology · 2024Review
- Carmofur prevents cell cycle progression by reducing E2F8 transcription in temozolomide-resistant glioblastoma cells.Cell death discovery · 2023Article
- Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells.Cancers · 2023Review
- Acid ceramidase involved in pathogenic cascade leading to accumulation of α-synuclein in iPSC model of GBA1-associated Parkinson's disease.Human molecular genetics · 2023Article
- Acid Ceramidase Deficiency: Bridging Gaps between Clinical Presentation, Mouse Models, and Future Therapeutic Interventions.Biomolecules · 2023Review
- Article
- Targeting the Sphingolipid Rheostat in Gliomas.International journal of molecular sciences · 2022Review
- Conformational Properties and Putative Bioactive Targets for Novel Thiosemicarbazone Derivatives.Molecules (Basel, Switzerland) · 2022Article
- Targeting Acid Ceramidase Inhibits Glioblastoma Cell Migration through Decreased AKT Signaling.Cells · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Human acid ceramidase (AC) is a lysosomal cysteine amidase, which has received a great deal of interest in recent years as a potential target for the development of new therapeutics against melanoma and glioblastoma tumors. Despite the strong interest in obtaining structural information, only the structures of the apo-AC enzyme in its zymogen and activated conformations are available. In this work, the crystal structure of AC in complex with the covalent carmofur inhibitor is presented. Carmofur is an antineoplastic drug containing an electrophilic carbonyl reactive group that targets the catalytic cysteine. This novel structural data explains the basis of the AC inhibition, provides insights into the enzymatic properties of the protein, and is a great aid toward the structure-based drug design of potent inhibitors for AC, providing the detailed mechanism, which has eluded the scientific community for more than 30 years, of carmofur's mysterious 5-fluorouracil-independent antitumor activity.
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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.