ArticleEuropean journal of medicinal chemistry2021
A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells.
Article in European journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 25 citations in OpenAlex.
- Development and Structural Characterization of UTE-156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A genome-scale drug discovery pipeline uncovers therapeutic targets and a unique p97 allosteric binding site inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Imidazole Hybrids: A Privileged Class of Heterocycles in Medicinal Chemistry with New Insights into Anticancer Activity.Molecules (Basel, Switzerland) · 2025Review
- A genome-scale drug discovery pipeline uncovers new therapeutic targets and a unique p97 allosteric binding site inbioRxiv : the preprint server for biology · 2025Article
- p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The AAA-ATPase Ter94 regulates wing size in Drosophila by suppressing the Hippo pathway.Communications biology · 2024Article
- Article
- Article
- Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases.Molecular neurodegeneration · 2023Review
- DNAJB6 isoform specific knockdown: Therapeutic potential for limb girdle muscular dystrophy D1.Molecular therapy. Nucleic acids · 2023Article
- The Cure VCP Scientific Conference 2021: Molecular and clinical insights into neurodegeneration and myopathy linked to multisystem proteinopathy-1 (MSP-1).Neurobiology of disease · 2022Review
- NMS-873 Leads to Dysfunctional Glycometabolism in A p97-Independent Manner in HCT116 Colon Cancer Cells.Pharmaceutics · 2022Article
- The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Conserved L464 in p97 D1-D2 linker is critical for p97 cofactor regulated ATPase activity.The Biochemical journal · 2021Article
- AAA ATPases as therapeutic targets: Structure, functions, and small-molecule inhibitors.European journal of medicinal chemistry · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Small-molecule inhibitors of p97 are useful tools to study p97 function. Human p97 is an important AAA ATPase due to its diverse cellular functions and implication in mediating the turnover of proteins involved in tumorigenesis and virus infections. Multiple p97 inhibitors identified from previous high-throughput screening studies are thiol-reactive compounds targeting Cys522 in the D2 ATP-binding domain. Thus, these findings suggest a potential strategy to develop covalent p97 inhibitors. We first used purified p97 to assay several known covalent kinase inhibitors to determine if they can inhibit ATPase activity. We evaluated their selectivity using our dual reporter cells that can distinguish p97 dependent and independent degradation. We selected a β-nitrostyrene scaffold to further study the structure-activity relationship. In addition, we used p97 structures to design and synthesize analogues of pyrazolo[3,4-d]pyrimidine (PP). We incorporated electrophiles into a PP-like compound 17 (4-amino-1-tert-butyl-3-phenyl pyrazolo[3,4-d]pyrimidine) to generate eight compounds. A selective compound 18 (N-(1-(tert-butyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)acrylamide, PPA) exhibited excellent selectivity in an in vitro ATPase activity assay: IC
Indexed as
Identifiers
What OpenQuestion holds
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.