ArticleLeukemia2013
F14512, a polyamine-vectorized anti-cancer drug, currently in clinical trials exhibits a marked preclinical anti-leukemic activity.
Article in Leukemia, 2013. 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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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
14 citing papers in PubMed, 35 citations in OpenAlex.
- Novel Water-Soluble, Heavy Atom-Free Thioxanthene-Fused Naphthalimide-Polyamine Phototheranostic Conjugates.ChemMedChem · 2026Article
- Biosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine.Nature communications · 2023Article
- Polyamine-Drug Conjugates: Do They Boost Drug Activity?Molecules (Basel, Switzerland) · 2023Review
- Nanomicelle-Microsphere Composite as a Drug Carrier to Improve Lung-Targeting Specificity for Lung Cancer.Pharmaceutics · 2022Article
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- Spermine modified polymeric micelles with pH-sensitive drug release for targeted and enhanced antitumor therapy.RSC advances · 2019Article
- Polyamine-containing etoposide derivatives as poisons of human type II topoisomerases: Differential effects on topoisomerase IIα and IIβ.Bioorganic & medicinal chemistry letters · 2018Article
- Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases.Current genomics · 2017Review
- Article
- Synthesis and Biological Evaluation of Novel Aromatic Imide-Polyamine Conjugates.Molecules (Basel, Switzerland) · 2016Article
- The role of VDR and BIM in potentiation of cytarabine-induced cell death in human AML blasts.Oncotarget · 2016Article
- Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates.Medicinal research reviews · 2016Review
- Activity of the polyamine-vectorized anti-cancer drug F14512 against pediatric glioma and neuroblastoma cell lines.Investigational new drugs · 2014Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapy remains mainly used for the treatment of acute myeloid leukemia (AML). However, in the past 3 decades limited progress has been achieved in improving the long-term disease-free survival. Therefore the development of more effective drugs for AML represents a high level of priority. F14512 combines an epipodophyllotoxin core targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. The polyamine moiety facilitates F14512 selective uptake by tumour cells via the polyamine transport system, a machinery overactivated in cancer cells. F14512 has been characterized as a potent drug candidate and is currently in Phase I clinical trials. Here, we demonstrated marked survival benefit and therapeutic efficacy of F14512 treatments in a series of human AML models, established either from AML cell lines or from patient AML samples. Furthermore, we reported in vitro synergistic anti-leukemic effects of F14512 in combination with cytosine arabinoside (Ara-C), doxorubicin, gemcitabine, bortezomib or SAHA. In vivo combination of suboptimal doses of F14512 with Ara-C also resulted in enhanced anti-leukemic activity. We further showed that F14512 triggered both senescence and apoptosis in vivo in primary AML models, but not autophagy. Overall, these results support the clinical development in onco-hematology of this novel promising drug candidate.
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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.