ArticleProceedings of the National Academy of Sciences of the United States of America2005
A small-molecule inhibitor of isoprenylcysteine carboxyl methyltransferase with antitumor activity in cancer cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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
87 citing papers in PubMed, 179 citations in OpenAlex.
- ICMT supports BRAFProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- The Dental and Oral Significance of Hutchinson-Gilford Prfogeria Syndrome : The Dental and Oral Significance of Hutchinson-Gilford Prfogeria Syndrome.Galen medical journal · 2025Review
- Targeting MDM2, RAS, and PCNA for cancer targeted therapy: pan-cancer approaches vs. cancer-specific strategies.Frontiers in pharmacology · 2025Review
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.Molecular diversity · 2024Review
- Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer.International journal of molecular sciences · 2024Review
- KRAS Mutation Subtypes and Their Association with Other Driver Mutations in Oncogenic Pathways.Cells · 2024Review
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review.World journal of gastrointestinal surgery · 2023Review
- Folylpolyglutamate synthetase mRNA G-quadruplexes regulate its cell protrusion localization and enhance a cancer cell invasive phenotype upon folate repletion.BMC biology · 2023Article
- Catalytic Cyanation of C-N Bonds with COJACS Au · 2022Article
- Targeting KRAS mutant cancers: from druggable therapy to drug resistance.Molecular cancer · 2022Review
- KRAS: A Druggable Target in Colon Cancer Patients.International journal of molecular sciences · 2022Review
- An In Vivo Inflammatory Loop Potentiates KRAS Blockade.Biomedicines · 2022Article
- Advances in Immunosuppressive Agents Based on Signal Pathway.Frontiers in pharmacology · 2022Review
- Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene.International journal of molecular sciences · 2021Review
- Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.Life science alliance · 2021Article
- Oncogenic KRAS: Signaling and Drug Resistance.Cancers · 2021Review
- Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer.Molecular cancer · 2021Review
27 more citing papers are in PubMed but not listed here.
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 3 institutions in 2 countries.
Funding
Abstract
Many key regulatory proteins, including members of the Ras family of GTPases, are modified at their C terminus by a process termed prenylation. This processing is initiated by the addition of an isoprenoid lipid, and the proteins are further modified by a proteolytic event and methylation of the C-terminal prenylcysteine. Although the biological consequences of prenylation have been characterized extensively, the contributions of prenylcysteine methylation to the functions of the modified proteins are not well understood. This reaction is catalyzed by the enzyme isoprenylcysteine carboxyl methyltransferase (Icmt). Recent genetic disruption studies have provided strong evidence that blocking Icmt activity has profound consequences on oncogenic transformation. Here, we report the identification of a selective small-molecule inhibitor of Icmt, 2-[5-(3-methylphenyl)-1-octyl-1H-indol-3-yl]acetamide (cysmethynil). Cysmethynil treatment results in inhibition of cell growth in an Icmt-dependent fashion, demonstrating mechanism-based activity of the compound. Treatment of cancer cells with cysmethynil results in mislocalization of Ras and impaired epidermal growth factor signaling. In a human colon cancer cell line, cysmethynil treatment blocks anchorage-independent growth, and this effect is reversed by overexpression of Icmt. These findings provide a compelling rationale for development of Icmt inhibitors as another approach to anticancer drug development.
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.