ArticlePloS one2015
VS-5584, a Novel PI3K-mTOR Dual Inhibitor, Inhibits Melanoma Cell Growth In Vitro and In Vivo.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Curcuminoids and Dimethoxycurcumin as Therapeutic Agents in Melanoma: Focus on Metastasis and Primary Care Integration.Cell biochemistry and function · 2026Review
- Cancer Stem Cells and the Renin-Angiotensin System in the Tumor Microenvironment of Melanoma: Implications on Current Therapies.International journal of molecular sciences · 2025Review
- Mechanisms and Therapeutic Strategies to Overcome Immune Checkpoint Inhibitor Resistance in Melanoma, Head and Neck, and Triple-Negative Breast Cancers.Journal of cellular immunology · 2025Article
- Kinase Inhibitors in Genetic Diseases.International journal of molecular sciences · 2023Review
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential.International journal of molecular sciences · 2022Review
- 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
- Review
- Rapamycin suppresses angiogenesis and lymphangiogenesis in melanoma by downregulating VEGF-A/VEGFR-2 and VEGF-C/VEGFR-3 expression.OncoTargets and therapy · 2019Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanomas cause over 76% of skin cancer deaths annually. Phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is important for melanoma initiation and progression. In the current study, we evaluated the potential anti-melanoma effect of VS-5584, a novel and highly potent PI3K-mTOR dual inhibitor. We demonstrated that VS-5584 potently inhibited survival and proliferation of established (A375, A-2058 and SK-MEL-3 lines) and primary human melanoma cells, but was non-cytotoxic to non-cancerous human skin keratinocytes and B10BR murine melanocytes. At the meantime, VS-5584 induced caspase-dependent apoptotic death in melanoma cells, and its cytotoxicity was alleviated by the caspase inhibitors. At the molecular level, VS-5584 blocked AKT-mTOR activation and downregulated cyclin D1 expression in melanoma cells, while the expressions of Bcl-xL and Bcl-2 were not affected by VS-5584 treatment. On the other hand, a BH-3 mimetic Bcl-xL/Bcl-2 inhibitor ABT-737, as well as siRNA-mediated knockdown of Bcl-xL or Bcl-2, enhanced the activity of VS-5584 in melanoma cells. In vivo, oral administration of VS-5584 suppressed A375 melanoma xenograft growth in nude mice, and its activity was further enhanced by co-administration of ABT-737. These results provide the rationale for the clinical assessment of VS-5584 in melanoma patients and development of ABT-737 and other Bcl-xL/Bcl-2 inhibitors as the possible adjuvants.
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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.