ArticleJournal of medicinal chemistry2019
Development of Novel Epoxyketone-Based Proteasome Inhibitors as a Strategy To Overcome Cancer Resistance to Carfilzomib and Bortezomib.
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 14 papers.
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Who cites it
14 citing papers in PubMed.
- Discovery of Novel Nonpeptidic Proteasome Inhibitors Using Covalent Virtual Screening and Biological Evaluation.ACS medicinal chemistry letters · 2024Article
- Primed for Interactions: Investigating the Primed Substrate Channel of the Proteasome for Improved Molecular Engagement.Molecules (Basel, Switzerland) · 2024Review
- Brain-Derived 11S Regulator (PA28αβ) Promotes Proteasomal Hydrolysis of Elongated Oligoglutamine-Containing Peptides.International journal of molecular sciences · 2023Article
- Influence ofInternational journal of molecular sciences · 2023Review
- Discovery of Novel Epoxyketone Peptides as Lipase Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism.International journal of molecular sciences · 2021Review
- Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease.Journal of medicinal chemistry · 2021Article
- A new class of α-ketoamide derivatives with potent anticancer and anti-SARS-CoV-2 activities.European journal of medicinal chemistry · 2021Article
- Article
- Proteasomal adaptations to FDA-approved proteasome inhibitors: a potential mechanism for drug resistance?Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Natural product scaffolds as inspiration for the design and synthesis of 20S human proteasome inhibitors.RSC chemical biology · 2020Article
- Ternary Polypeptide Nanoparticles with Improved Encapsulation, Sustained Release, and Enhanced In Vitro Efficacy of Carfilzomib.Pharmaceutical research · 2020Article
- Parthenolide inhibits ubiquitin-specific peptidase 7 (USP7), Wnt signaling, and colorectal cancer cell growth.The Journal of biological chemistry · 2020Article
- Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5.Molecules (Basel, Switzerland) · 2019Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Over the past 15 years, proteasome inhibitors (PIs), namely bortezomib, carfilzomib (Cfz) and ixazomib, have significantly improved the overall survival and quality-of-life for multiple myeloma (MM) patients. However, a significant portion of MM patients do not respond to PI therapies. Drug resistance is present either de novo or acquired after prolonged therapy through mechanisms that remain poorly defined. The lack of a clear understanding of clinical PI resistance has hampered the development of next-generation PI drugs to treat MM patients who no longer respond to currently available therapies. Here, we designed and synthesized novel epoxyketone-based PIs by structural modifications at the P1' site. We show that a Cfz analog, 9, harboring a hydroxyl substituent at its P1' position was highly cytotoxic against cancer cell lines displaying de novo or acquired resistance to Cfz. These results suggest that peptide epoxyketones incorporating P1'-targeting moieties may have the potential to bypass resistance mechanisms associated with Cfz and to provide additional clinical options for patients resistant to Cfz.
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Registered trials
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