ArticleInvestigational new drugs2000
UCN-01 enhances the in vitro toxicity of clinical agents in human tumor cell lines.
Article in Investigational new drugs, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 74 citations in OpenAlex.
- A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2013Trial
- The Multifaceted Role of p53 in Cancer Molecular Biology: Insights for Precision Diagnosis and Therapeutic Breakthroughs.Biomolecules · 2025Review
- Selective inhibition of DNA ligase IV provides additional efficacy to the treatment of anaplastic thyroid cancer.Frontiers in oncology · 2024Article
- Computationally prioritized drugs inhibit SARS-CoV-2 infection and syncytia formation.Briefings in bioinformatics · 2022Article
- Article
- UCN-SiORSC advances · 2018Article
- Centromere fragmentation is a common mitotic defect of S and G2 checkpoint override.Cell cycle (Georgetown, Tex.) · 2013Article
- Phase I trial of 7-hydroxystaurosporine and fludararbine phosphate: in vivo evidence of 7-hydroxystaurosporine induced apoptosis in chronic lymphocytic leukemia.Leukemia & lymphoma · 2011Article
- Article
- p53-dependent G(1) arrest in 1st or 2nd cell cycle may protect human cancer cells from cell death after treatment with ionizing radiation and Chk1 inhibitors.Cell proliferation · 2010Article
- A phase I trial of UCN-01 and prednisone in patients with refractory solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2010Article
- Cyclin-dependent kinase inhibitors as potential targeted anticancer agents.Investigational new drugs · 2009Review
- Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells.Neoplasia (New York, N.Y.) · 2009Article
- Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in patients with solid tumors.Cancer chemotherapy and pharmacology · 2008Article
- AG490 influences UCN-01-induced cytotoxicity in glioma cells in a p53-dependent fashion, correlating with effects on BAX cleavage and BAD phosphorylation.Cancer letters · 2007Article
- The intra-S-phase checkpoint affects both DNA replication initiation and elongation: single-cell and -DNA fiber analyses.Molecular and cellular biology · 2007Article
- Article
- Article
- Review
- Issues and progress with protein kinase inhibitors for cancer treatment.Nature reviews. Drug discovery · 2003Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
UCN-01 is undergoing Phase I evaluation and is a candidate for combination strategies in the clinic. UCN-01 has been shown to have a variety of effects on cellular targets and the cell cycle. It has also been reported to sensitize cells to several clinical drugs in vitro, possibly in a manner related to p53 status. Thus, combinations of UCN-01 with a series of clinical agents in variety of cell lines have been investigated in vitro. Certain cell lines demonstrated synergistic interactions with combinations of UCN-01 (20-150 nM) and thiotepa, mitomycin C, cisplatin, melphalan, topotecan, gemcitabine, fludarabine or 5-fluorouracil. In contrast, UCN-01 combinations with the antimitotic agents, paclitaxel and vincristine, or topoisomerase II inhibitors, adriamycin and etoposide, did not result in synergy, only in additive toxicity. Cells with non-functional p53 were significantly more susceptible to the supra-additive effects of certain DNA-damaging agents and UCN-01 combinations, than cells expressing functional p53 activity. In contrast, there was no significant relationship between p53 status and susceptibility to synergy between antimetabolites and UCN-01. The mechanism behind the observed synergy appeared unrelated to effects on protein kinase C or abrogation of the cell cycle in G2. Moreover, increased apoptosis did not fully explain the supradditive response. These data indicate that UCN-01 sensitizes a variety of cell lines to certain DNA-damaging agents (frequently covalent DNA-binding drugs) and antimetabolites in vitro, but the mechanism underlying this interaction remains undefined.
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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.