ArticleJournal of medicinal chemistry2009
Lipophilic lysine-spermine conjugates are potent polyamine transport inhibitors for use in combination with a polyamine biosynthesis inhibitor.
Article in Journal of medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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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
47 citing papers in PubMed, 96 citations in OpenAlex.
- Phase I/II clinical trial of 2-difluoromethyl-ornithine (DFMO) and a novel polyamine transport inhibitor (MQT 1426) for feline oral squamous cell carcinoma.Veterinary and comparative oncology · 2011Trial
- Metabolic reprogramming in cancer: signaling pathways and therapeutic targets.Molecular cancer · 2026Review
- Article
- Genetically encoded fluorescent reporter for polyamines.Nature communications · 2025Article
- The polyamine transporter ATP13A3 mediates difluoromethylornithine-induced polyamine uptake in neuroblastoma.Molecular oncology · 2025Article
- Malignant epithelia cells-derived spermine induces APOE+ macrophages to suppress tumor immunity in adenocarcinoma of the esophagogastric junction.Frontiers in medicine · 2025Article
- Polyamine metabolism and anti-tumor immunity.Frontiers in immunology · 2025Review
- The Synergistic Benefit of Combination Strategies Targeting Tumor Cell Polyamine Homeostasis.International journal of molecular sciences · 2024Review
- Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.Cell death and differentiation · 2024Article
- Glioma Metabolic Feedback In Situ: A First-In-Human Pharmacodynamic Trial of Difluoromethylornithine + AMXT-1501 Through High-Molecular Weight Microdialysis.Neurosurgery · 2023Article
- Article
- Arginine metabolism regulates human erythroid differentiation through hypusination of eIF5A.Blood · 2023Article
- Article
- One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.Biomolecules · 2022Review
- Histone deacetylase-10 liberates spermidine to support polyamine homeostasis and tumor cell growth.The Journal of biological chemistry · 2022Article
- Polyamines in cancer: integrating organismal metabolism and antitumour immunity.Nature reviews. Cancer · 2022Review
- Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism.Cancer research communications · 2022Article
- Molecular Pathways Involved in the Anti-Cancer Activity of Flavonols: A Focus on Myricetin and Kaempferol.International journal of molecular sciences · 2022Review
- Development of Polyamine Lassos as Polyamine Transport Inhibitors.ACS medicinal chemistry letters · 2022Article
- Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells.Cell reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cancer cells can overcome the ability of polyamine biosynthesis inhibitors to completely deplete their internal polyamines by the importation of polyamines from external sources. This paper discusses the development of a group of lipophilic polyamine analogues that potently inhibit the cellular polyamine uptake system and greatly increase the effectiveness of polyamine depletion when used in combination with DFMO, a well-studied polyamine biosynthesis inhibitor. The attachment of a length-optimized C(16) lipophilic substituent to the epsilon-nitrogen atom of an earlier lead compound, D-Lys-Spm (5), has produced an analogue, D-Lys(C(16)acyl)-Spm (11) with several orders of magnitude more potent cell growth inhibition on a variety of cultured cancer cell types including breast (MDA-MB-231), prostate (PC-3), melanoma (A375), and ovarian (SK-OV-3), among others. These results are discussed in the context of a possible membrane-catalyzed interaction with the extracellular polyamine transport apparatus. The resulting novel two-drug combination therapy targeting cellular polyamine metabolism has shown exceptional efficacy against cutaneous squamous cell carcinomas (SCC) in a transgenic ornithine decarboxylase (ODC) mouse model of skin cancer. A majority (88%) of large, aggressive SCCs exhibited complete or nearly complete remission to this combination therapy, whereas responses to each agent alone were poor. The availability of a potent polyamine transport inhibitor allows, for the first time, for a real test of the hypothesis that starving cells of polyamines will lead to objective clinical response.
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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.