ArticleJournal of biomolecular screening2007
Small-molecule inhibitors of the Rce1p CaaX protease.
Article in Journal of biomolecular screening, 2007. 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 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.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- Targeted genetic and small molecule disruption of N-Ras CaaX cleavage alters its localization and oncogenic potential.Bioorganic chemistry · 2024Article
- Defective synaptic plasticity in a model of Coffin-Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene.International journal of molecular sciences · 2021Review
- Scaffold repurposing of fendiline: Identification of potent KRAS plasma membrane localization inhibitors.European journal of medicinal chemistry · 2021Article
- Ste24: An Integral Membrane Protein Zinc Metalloprotease with Provocative Structure and Emergent Biology.Journal of molecular biology · 2020Review
- TargetingInternational journal of molecular sciences · 2020Review
- KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?Cancer treatment reviews · 2020Review
- Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting.Seminars in cancer biology · 2019Review
- Phosphoramidon inhibits the integral membrane protein zinc metalloprotease ZMPSTE24.Acta crystallographica. Section D, Structural biology · 2018Article
- Rce1: mechanism and inhibition.Critical reviews in biochemistry and molecular biology · 2018Review
- Acquisition of accurate data from intramolecular quenched fluorescence protease assays.Analytical biochemistry · 2017Article
- Targeting the KRAS Pathway in Non-Small Cell Lung Cancer.The oncologist · 2016Review
- A shunt pathway limits the CaaX processing of Hsp40 Ydj1p and regulates Ydj1p-dependent phenotypes.eLife · 2016Article
- Ste24p Mediates Proteolysis of Both Isoprenylated and Non-prenylated Oligopeptides.The Journal of biological chemistry · 2016Article
- The renewed battle against RAS-mutant cancers.Cellular and molecular life sciences : CMLS · 2016Review
- 8-Hydroxyquinoline-based inhibitors of the Rce1 protease disrupt Ras membrane localization in human cells.Bioorganic & medicinal chemistry · 2016Article
- Targeting RAS Membrane Association: Back to the Future for Anti-RAS Drug Discovery?Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- Drugging the undruggable RAS: Mission possible?Nature reviews. Drug discovery · 2014Review
- A RAS renaissance: emerging targeted therapies for KRAS-mutated non-small cell lung cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Rce1p protease is required for the maturation of the Ras GTPase and certain other isoprenylated proteins and is considered a chemotherapeutic target. To identify new small-molecule inhibitors of Rce1p, the authors screened the National Cancer Institute Diversity Set compound library using in vitro assays to monitor the proteolytic processing of peptides derived from Ras and the yeast a-factor mating pheromone. Of 46 inhibitors initially identified with a Ras-based assay, only 9 were effective in the pheromone-based assay. The IC(50) values of these 9 compounds were in the low micromolar range for both yeast (6-35 microM) and human Rce1p (0.4-46 microM). Four compounds were somewhat Rce1p selective in that they partially inhibited the Ste24p protease and did not inhibit Ste14p isoprenylcysteine carboxyl methyltransferase, 2 enzymes also involved in the maturation of isoprenylated proteins. The remaining 5 compounds inhibited all 3 enzymes. The 2 most Rce1p-selective agents were ineffective trypsin inhibitors, further supporting the specificity of these agents for Rce1p. The 5 least specific compounds formed colloidal aggregates, a proposed common feature of promiscuous inhibitors. Interestingly, the most specific Rce1p inhibitor also formed a colloidal aggregate. In vivo studies revealed that treatment of wild-type yeast with 1 compound induced a Ras2p delocalization phenotype that mimics observed effects in rce1 ste24 null yeast. The 9 compounds identified in this study represent new tools for understanding the enzymology of postisoprenylation-modifying enzymes and provide new insight for the future development of Rce1p 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.