ArticleScientific reports2017
A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Structural basis for a p21-activated kinase 4 and nicotinamide phosphoribosyltransferase dual inhibitor.Acta crystallographica. Section D, Structural biology · 2026Article
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 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
- P21-activated kinase 4: a potent oncogene, molecular mechanisms and opportunities for targeted therapy.Cancer cell international · 2025Review
- Identification of Potential Selective PAK4 Inhibitors Through Shape and Protein Conformation Ensemble Screening and Electrostatic-Surface-Matching Optimization.Current issues in molecular biology · 2025Article
- Design, synthesis and pharmacological evaluation of 1,2,3,4-tetrahydrobenzofuro[2,3-Acta pharmaceutica Sinica. B · 2025Article
- Application of Artificial Intelligence-Based Approaches in the Discovery and Development of Protein Kinase Inhibitors (PKIs) Targeting Anticancer Activity.Current topics in medicinal chemistry · 2025Review
- Comprehensive multi-omics analysis identifies NUSAP1 as a potential prognostic and immunotherapeutic marker for lung adenocarcinoma.International journal of medical sciences · 2025Article
- Inhibition of NAMPT by PAK4 Inhibitors.International journal of molecular sciences · 2024Article
- Identification of a glycolysis-related miRNA Signature for Predicting Breast cancer Survival.Molecular biotechnology · 2024Article
- Tumorigenic role of Pak4 in ovarian cancer and its correlation with immune infiltration.BMC medical genomics · 2024Article
- Recent advances in multitarget-directed ligands via in silico drug discovery.Drug discovery today · 2024Review
- The role of p21-activated kinase 4 in the progression of oral squamous cell carcinoma by targeting PI3K-AKT signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Article
- Rho family GTPase signaling through type II p21-activated kinases.Cellular and molecular life sciences : CMLS · 2022Review
- Remodeling of the tumor microenvironment through PAK4 inhibition sensitizes tumors to immune checkpoint blockade.Cancer research communications · 2022Article
- NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets.International journal of molecular sciences · 2022Review
- Review
- Dual Function of Secreted APE1/Ref-1 in TNBC Tumorigenesis: An Apoptotic Initiator and a Regulator of Chronic Inflammatory Signaling.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is a heterogeneous disease consisting of several subtypes. Among these subtypes, triple negative breast cancer is particularly difficult to treat. This is due to a lack of understanding of the mechanisms behind the disease, and consequently a lack of druggable targets. PAK4 plays critical roles in cell survival, proliferation, and morphology. PAK4 protein levels are high in breast cancer cells and breast tumors, and the gene is often amplified in basal like breast cancers, which are frequently triple negative. PAK4 is also overexpressed in other types of cancer, making it a promising drug target. However, its inhibition is complicated by the fact that PAK4 has both kinase-dependent and -independent functions. Here we investigate a new clinical compound KPT-9274, which has been shown to inhibit PAK4 and NAMPT. We find that KPT-9274 (and its analog, KPT-8752) can reduce the steady state level of PAK4 protein in triple negative breast cancer cells. These compounds also block the growth of the breast cancer cells in vitro, and stimulate apoptosis. Most importantly, oral administration of KPT-9274 reduces tumorigenesis in mouse models of human triple negative breast cancer. Our results indicate that KPT-9274 is a novel therapeutic option for triple negative breast cancer therapy.
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