ArticleMolecular cancer therapeutics2010
A novel small-molecule inhibitor of protein kinase D blocks pancreatic cancer growth in vitro and in vivo.
Article in Molecular cancer therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 122 papers.
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Who cites it
122 citing papers in PubMed, 171 citations in OpenAlex.
- Mechanical forces stimulate Golgi export.The Journal of cell biology · 2026Article
- Dynamic visualization of physiological CaMKII activity using sensitive FRET biosensors.bioRxiv : the preprint server for biology · 2026Article
- Protein Kinase D2 Regulates GRASP65 Phosphorylation and Golgi Ribbon Unlinking During G2/M Transition.Cells · 2026Article
- Spatial single-cell profiling identifies protein kinase Cδ-expressing microglia with anti-tumor function in glioblastoma.iScience · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Golgi Retention and Oncogenic Signaling of KIT Tyrosine Kinase in Gastrointestinal Stromal Tumor.Sub-cellular biochemistry · 2026Review
- Golgi Drivers of Cancer.Sub-cellular biochemistry · 2026Review
- Activation of the Piezo1 channel stimulates protein kinase D and migration in human aortic endothelial cells.American journal of physiology. Cell physiology · 2025Article
- Effect of PRKD3 on cell cycle in gastric cancer progression and downstream regulatory networks.Medical oncology (Northwood, London, England) · 2025Article
- Stress and Obesity Signaling Converge on CREB Phosphorylation to Promote Pancreatic Cancer.Molecular cancer research : MCR · 2025Article
- Targeting adipocyte differentiation with CRT0066101: activation of AMPK signaling in 3T3-L1 cells.Frontiers in pharmacology · 2025Article
- A Novel Gene Fusion YLPM1::PRKD1 Identified in a Cribriform Subtype of Polymorphous Adenocarcinoma.Head and neck pathology · 2024Article
- PKCμ promotes keratinocyte cell migration through Cx43 phosphorylation-mediated suppression of intercellular communication.iScience · 2024Article
- Protein kinase D1 - A targetable mediator of pancreatic cancer development.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Protein kinase D2 confers neuroprotection by promoting AKT and CREB activation in ischemic stroke.Neurobiology of disease · 2023Article
- Structural insights into regulation of the PEAK3 pseudokinase scaffold by 14-3-3.Nature communications · 2023Article
- Review
- Protein Kinase D2 and D3 Promote Prostate Cancer Cell Bone Metastasis by Positively Regulating Runx2 in a MEK/ERK1/2-Dependent Manner.The American journal of pathology · 2023Article
- Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.American journal of physiology. Cell physiology · 2023Article
- A specific anti-cyclin D1 intrabody represses breast cancer cell proliferation by interrupting the cyclin D1-CDK4 interaction.Breast cancer research and treatment · 2023Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
- Correction · 2010-07-01Error in Text ·
- Erratum issuedBagherazadeh, Azadeh [corrected to Bagherzadeh, Azadeh]
Authors and funding
26 authors at 1 institution in 1 country.
Funding
Abstract
Protein kinase D (PKD) family members are increasingly implicated in multiple normal and abnormal biological functions, including signaling pathways that promote mitogenesis in pancreatic cancer. However, nothing is known about the effects of targeting PKD in pancreatic cancer. Our PKD inhibitor discovery program identified CRT0066101 as a specific inhibitor of all PKD isoforms. The aim of our study was to determine the effects of CRT0066101 in pancreatic cancer. Initially, we showed that autophosphorylated PKD1 and PKD2 (activated PKD1/2) are significantly upregulated in pancreatic cancer and that PKD1/2 are expressed in multiple pancreatic cancer cell lines. Using Panc-1 as a model system, we showed that CRT0066101 reduced bromodeoxyuridine incorporation; increased apoptosis; blocked neurotensin-induced PKD1/2 activation; reduced neurotensin-induced, PKD-mediated Hsp27 phosphorylation; attenuated PKD1-mediated NF-kappaB activation; and abrogated the expression of NF-kappaB-dependent proliferative and prosurvival proteins. We showed that CRT0066101 given orally (80 mg/kg/d) for 24 days significantly abrogated pancreatic cancer growth in Panc-1 subcutaneous xenograft model. Activated PKD1/2 expression in the treated tumor explants was significantly inhibited with peak tumor concentration (12 micromol/L) of CRT0066101 achieved within 2 hours after oral administration. Further, we showed that CRT0066101 given orally (80 mg/kg/d) for 21 days in Panc-1 orthotopic model potently blocked tumor growth in vivo. CRT0066101 significantly reduced Ki-67-positive proliferation index (P < 0.01), increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive apoptotic cells (P < 0.05), and abrogated the expression of NF-kappaB-dependent proteins including cyclin D1, survivin, and cIAP-1. Our results show for the first time that a PKD-specific small-molecule inhibitor CRT0066101 blocks pancreatic cancer growth in vivo and show that PKD is a novel therapeutic target in pancreatic cancer.
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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.