ArticleChemMedChem2020
Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy.
Article in ChemMedChem, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
- The Autophagic Interaction Between p97/VCP and ABP Protein Expressions in Sertoli Cell Line: the Effects of Chloroquine and Rapamycin.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Article
- p97/VCP as a dual regulator of UPS and autophagy in ovarian cancer: a novel therapeutic target.Journal of molecular histology · 2026Article
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- VCP's nuclear journey: Initiated by interacting with KPNB1 to repair DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- The NRF2-p97-NRF2 negative feedback loop.Redox biology · 2023Article
- Article
- Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2023Article
- Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases.Biomolecules · 2023Review
- Common Markers and Small Molecule Inhibitors in Golgi Studies.Methods in molecular biology (Clifton, N.J.) · 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
- Temporal proteomics reveal specific cell cycle oncoprotein downregulation by p97/VCP inhibition.Cell chemical biology · 2022Article
- The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation.Pharmaceuticals (Basel, Switzerland) · 2022Article
- A targeted covalent inhibitor of p97 with proteome-wide selectivity.Acta pharmaceutica Sinica. B · 2022Article
- Article
- Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOBiomolecules · 2021Article
- 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
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
A major challenge of targeted cancer therapy is the selection for drug-resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is central regulator of protein homeostasis and a promising anticancer target because of its vital role in cell growth and survival. One ATP-competitive p97 inhibitor, CB-5083, has entered clinical trials. Selective pressure on HCT116 cells dosed with CB-5083 identified five different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB-5083 resistant p97 mutants, N660 K and T688 A, were also resistant to several other ATP-competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS-873 and UPCDC-30245 were unaffected by these mutations. We also established a CB-5083 resistant cell line that harbors a new p97 double mutation (D649 A/T688 A). While CB-5083, NMS-873, and UPCDC-30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS-873 and UPCDC-30245 were 30-fold more potent in inhibiting the CB-5083 resistant D649 A/T688 A double mutant than CB-5083. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP-competitive p97 inhibitors arises during anticancer treatment.
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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.