ArticleChemical research in toxicology2020
KPT-9274, an Inhibitor of PAK4 and NAMPT, Leads to Downregulation of mTORC2 in Triple Negative Breast Cancer Cells.
Article in Chemical research in toxicology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 38 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- First-in-Human Phase I Study of KPT-9274, a First-in-Class Dual Inhibitor of PAK4 and NAMPT, in Patients with Advanced Solid Malignancies.Targeted oncology · 2026Article
- Article
- Nuclear-Cytoplasmic Axis in Cancer: From Protein Mislocalization to Anticancer Drug Resistance.Oncology research · 2026Review
- Targeting TRAF3IP2 disrupts cellular energetics through inhibition of NAMPT in triple negative breast cancer.Scientific reports · 2025Article
- Identification of Potential Selective PAK4 Inhibitors Through Shape and Protein Conformation Ensemble Screening and Electrostatic-Surface-Matching Optimization.Current issues in molecular biology · 2025Article
- Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.International journal of medical sciences · 2025Article
- Molecular Characterization and Clinical Outcomes of Pancreatic Neuroendocrine Neoplasms Harboring PAK4-NAMPT Alterations.JCO oncology advances · 2025Article
- Inhibition of NAMPT by PAK4 Inhibitors.International journal of molecular sciences · 2024Article
- Channeling Nicotinamide Phosphoribosyltransferase (NAMPT) to Address Life and Death.Journal of medicinal chemistry · 2024Review
- P-21 Activated Kinases in Liver Disorders.Cancers · 2023Review
- Altered Adipokine Expression in Tumor Microenvironment Promotes Development of Triple Negative Breast Cancer.Cancers · 2022Review
- Phosphoproteomic Analysis of Breast Cancer-Derived Small Extracellular Vesicles Reveals Disease-Specific Phosphorylated Enzymes.Biomedicines · 2022Article
- Recent advances on development of p21-activated kinase 4 inhibitors as anti-tumor agents.Frontiers in pharmacology · 2022Review
- Review
- PAK4-NAMPT Dual Inhibition Sensitizes Pancreatic Neuroendocrine Tumors to Everolimus.Molecular cancer therapeutics · 2021Article
- Regulation and metabolic functions of mTORC1 and mTORC2.Physiological reviews · 2021Review
- Advances in NAD-Lowering Agents for Cancer Treatment.Nutrients · 2021Review
- The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?Frontiers in cell and developmental biology · 2021Review
- NADSignal transduction and targeted therapy · 2021Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Triple negative breast cancer (TNBC) is difficult to treat due to lack of druggable targets. We have found that treatment with the small molecule inhibitor KPT-9274 inhibits growth of TNBC cells and eventually leads to cell death. KPT-9274 is a dual specific inhibitor of PAK4 and Nicotinamide Phosphoribosyltransferase (NAMPT). The PAK4 protein kinase is often highly expressed in TNBC cells and has important roles in cell growth, survival, and migration. Previously we have found that inhibition of PAK4 leads to growth inhibition of TNBC cells both in vitro and in vivo. Likewise, NAMPT has been shown to be dysregulated in cancer due to its role in cell metabolism. In order to understand better how treating cells with KPT-9274 abrogates TNBC cell growth, we carried out an RNA sequencing of TNBC cells treated with KPT-9274. As a result, we identified Rictor as an important target that is inhibited in the KPT-9274 treated cells. Conversely, we found that Rictor is predicted to be activated when PAK4 is overexpressed in cells, which suggests a role for PAK4 in the regulation of Rictor. Rictor is a component of mTORC2, one of the complexes formed by the serine/threonine kinase mTOR. mTOR is important for the control of cell growth and metabolism. Our results suggest a new mechanism by which the KPT-9274 compound may block the growth of breast cancer cells, which is via inhibition of mTORC2 signaling. Consistent with this, sequencing analysis of PAK4 overexpressing cells indicates that PAK4 has a role in activation of the mTOR pathway.
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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.