ArticleMolecular cancer therapeutics2013
VS-5584, a novel and highly selective PI3K/mTOR kinase inhibitor for the treatment of cancer.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 71 citations in OpenAlex.
- Targeting PI3K family with small-molecule inhibitors in cancer therapy: current clinical status and future directions.Molecular cancer · 2024Review
- Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing.International journal of molecular sciences · 2023Article
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Selectively Targeting Breast Cancer Stem Cells by 8-Quinolinol and Niclosamide.International journal of molecular sciences · 2022Article
- Wnt and PI3K/Akt/mTOR Survival Pathways as Therapeutic Targets in Glioblastoma.International journal of molecular sciences · 2022Review
- Treatment Strategies Against Triple-Negative Breast Cancer: An Updated Review.Breast cancer (Dove Medical Press) · 2022Review
- Recent Advances in Dual PI3K/mTOR Inhibitors for Tumour Treatment.Frontiers in pharmacology · 2022Review
- Inhibitors of the PI3K/Akt/mTOR Pathway in Prostate Cancer Chemoprevention and Intervention.Pharmaceutics · 2021Review
- Antitumor activity and mechanism of resistance of the novel HDAC and PI3K dual inhibitor CUDC-907 in pancreatic cancer.Cancer chemotherapy and pharmacology · 2021Article
- Evodiamine Inhibits Gastric Cancer Cell ProliferationEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Development of a UPLC-MS/MS Method for the Quantification of VS-5584 and Its Application in Pharmacokinetic Studies in Rats.Journal of analytical methods in chemistry · 2020Article
- Identification of plicamycin, TG02, panobinostat, lestaurtinib, and GDC-0084 as promising compounds for the treatment of central nervous system infections caused by the free-living amebae Naegleria, Acanthamoeba and Balamuthia.International journal for parasitology. Drugs and drug resistance · 2019Article
- Modulator of the PI3K/Akt oncogenic pathway affects mTOR complex 2 in human adenocarcinoma cells.Investigational new drugs · 2019Article
- Combination Therapy with a PI3K/mTOR Dual Inhibitor and Chloroquine Enhances Synergistic Apoptotic Cell Death in Epstein-Barr Virus-Infected Gastric Cancer Cells.Molecules and cells · 2019Article
- Targeting BCR-ABL-Independent TKI Resistance in Chronic Myeloid Leukemia by mTOR and Autophagy Inhibition.Journal of the National Cancer Institute · 2018Article
- VS-5584 mediates potent anti-myeloma activity via the upregulation of a class II tumor suppressor gene, RARRES3 and the activation of Bim.Oncotarget · 2017Article
- Recent advances in the use of PI3K inhibitors for glioblastoma multiforme: current preclinical and clinical development.Molecular cancer · 2017Review
- The mTOR pathway in obesity driven gastrointestinal cancers: Potential targets and clinical trials.BBA clinical · 2016Review
- Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma.Scientific reports · 2016Article
- Judicious Toggling of mTOR Activity to Combat Insulin Resistance and Cancer: Current Evidence and Perspectives.Frontiers in pharmacology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC(50) = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC(50): PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials.
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.