ArticleCancer biology & therapy2014
An improved isoprenylcysteine carboxylmethyltransferase inhibitor induces cancer cell death and attenuates tumor growth in vivo.
Article in Cancer biology & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Targeting ICMT: A promising strategy in cancer treatment (Review).Oncology letters · 2026Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 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
- Complete genome sequence ofMicrobiology resource announcements · 2024Article
- Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.Nature reviews. Cancer · 2024Review
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Article
- CircRNA hsa_circ_0018289 exerts an oncogenic role in cervical cancer progression through miR-1294/ICMT axis.Journal of clinical laboratory analysis · 2022Article
- Isoprenylcysteine carboxyl methyltransferase is critical for glioblastoma growth and survival by activating Ras/Raf/Mek/Erk.Cancer chemotherapy and pharmacology · 2022Article
- The wide and growing range of lamin B-related diseases: from laminopathies to cancer.Cellular and molecular life sciences : CMLS · 2022Review
- Suppression of isoprenylcysteine carboxylmethyltransferase compromises DNA damage repair.Life science alliance · 2021Article
- Post-translational modification of KRAS: potential targets for cancer therapy.Acta pharmacologica Sinica · 2021Review
- Review
- MicroRNA-99a-5p suppresses cell proliferation, migration, and invasion by targeting isoprenylcysteine carboxylmethyltransferase in oral squamous cell carcinoma.The Journal of international medical research · 2021Article
- Article
- Effects of isoprenylcysteine carboxyl methyltransferase silencing on the proliferation and apoptosis of tongue squamous cell carcinoma.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Article
- Blocking K-Ras Interaction With the Plasma Membrane Is a Tractable Therapeutic Approach to Inhibit Oncogenic K-Ras Activity.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of isoprenylcysteine carboxylmethyltransferase (Icmt) are promising anti-cancer agents, as modification by Icmt is an essential component of the protein prenylation pathway for a group of proteins that includes Ras GTPases. Cysmethynil, a prototypical indole-based inhibitor of Icmt, effectively inhibits tumor cell growth. However, the physical properties of cysmethynil, such as its low aqueous solubility, make it a poor candidate for clinical development. A novel amino-derivative of cysmethynil with superior physical properties and marked improvement in efficacy, termed compound 8.12, has recently been reported. We report here that Icmt (-/-) mouse embryonic fibroblasts (MEFs) are much more resistant to compound 8.12-induced cell death than their wild-type counterparts, providing evidence that the anti-proliferative effects of this compound are mediated through an Icmt specific mechanism. Treatment of PC3 prostate and HepG2 liver cancer cells with compound 8.12 resulted in pre-lamin A accumulation and Ras delocalization from the plasma membrane, both expected outcomes from inhibition of the Icmt-catalyzed carboxylmethylation. Treatment with compound 8.12 induced cell cycle arrest, autophagy and cell death, and abolished anchorage-independent colony formation. Consistent with its greater in vitro efficacy, compound 8.12 inhibited tumor growth with greater potency than cysmethynil in a xenograft mouse model. Further, a drug combination study identified synergistic antitumor efficacy of compound 8.12 and the epithelial growth factor receptor (EGFR)-inhibitor gefitinib, possibly through enhancement of autophagy. This study establishes compound 8.12 as a pharmacological inhibitor of Icmt that is an attractive candidate for further preclinical and clinical development.
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