ArticleMolecular pharmacology2019
Structural Basis of p97 Inhibition by the Site-Selective Anticancer Compound CB-5083.
Article in Molecular pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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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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.
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Who cites it
38 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Article
- Development and Structural Characterization of UTE-156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting VCP with V8 suppresses glioblastoma development via formation of aggregates and disruption of mitophagy flux.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Induced ubiquitination bypasses canonical ERAD to drive ER protein degradation.bioRxiv : the preprint server for biology · 2025Article
- Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.Journal of cell science · 2024Article
- VCP enhances autophagy-related osteosarcoma progression by recruiting USP2 to inhibit ubiquitination and degradation of FASN.Cell death & disease · 2024Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- Valosin-Containing Protein (VCP)/p97 Oligomerization.Sub-cellular biochemistry · 2024Review
- Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases.Biomolecules · 2023Review
- Discovery of novel benzylquinazoline molecules as p97/VCP inhibitors.Frontiers in pharmacology · 2023Article
- Bcs1, a novel target for fungicide.Frontiers in chemistry · 2023Review
- Fragment screening using biolayer interferometry reveals ligands targeting the SHP-motif binding site of the AAA+ ATPase p97.Communications chemistry · 2022Article
- Two-in-One Nanoparticle Formulation to Deliver a Tyrosine Kinase Inhibitor and microRNA for Targeting Metabolic Reprogramming and Mitochondrial Dysfunction in Gastric Cancer.Pharmaceutics · 2022Article
- Cryo-EM structures of human p97 double hexamer capture potentiated ATPase-competent state.Cell discovery · 2022Article
- Pharmacological targeting of endoplasmic reticulum stress in disease.Nature reviews. Drug discovery · 2022Review
- Article
- The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.Nature cell biology · 2022Article
- Cryo-electron microscopy structures of VCP/p97 reveal a new mechanism of oligomerization regulation.iScience · 2021Article
- Targeting allostery in the Dynein motor domain with small molecule inhibitors.Cell chemical biology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Inhibition of p97, a key player in the ubiquitin-proteasome degradation pathway, has been proposed as a treatment of cancer. This concept was nearly realized recently when a potent p97 inhibitor, 1-[4-(benzylamino)-5H,7H,8H-pyrano[4,3-d]pyrimidin-2-yl]-2-methyl-1H-indole-4-carboxamide (CB-5083), was developed and demonstrated broad antitumor activity in various tumor models. CB-5083 functions as a competitive inhibitor that binds selectively to the ATP-binding site of the D2 domain, although both the D1 and D2 ATPase sites of p97 are highly similar. Despite its promising anticancer activity, CB-5083 failed its phase I clinical trials due to an unexpected off-target effect, which necessitates further improvement of the inhibitor. In this study, we determined the crystal structure of N-terminal domain-truncated p97 in complex with CB-5083. It provides a structural basis for the specificity of CB-5083 toward the D2 domain, offers an explanation in atomic detail for the mutations that confer resistance to CB-5083, and establishes a foundation for future structure-guided efforts to develop the next generation of p97 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.