ArticlePloS one2013
New pyrazolopyrimidine inhibitors of protein kinase d as potent anticancer agents for prostate cancer cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Bulky PP1 analogs exert cellular effects independently from analog-sensitive kinase inhibition.Frontiers in chemistry · 2026Article
- Targeting bacterial kinases as a strategy to counteract antibiotic resistance.Communications chemistry · 2025Article
- Methylstat sensitizes ovarian cancer cells to PARP-inhibition by targeting the histone demethylases JMJD1B/C.Cancer gene therapy · 2025Article
- A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer.Molecular cancer therapeutics · 2024Article
- Regioselective Synthesis of Cycloalkane-fused Pyrazolo[4,3-Current organic synthesis · 2024Article
- ATP Consumption Is Coupled with Endocytosis in Exudated Neutrophils.International journal of molecular sciences · 2023Article
- Design, Synthesis and Biological Evaluation of Novel Pleuromutilin Derivatives Containing 6-Chloro-1-R-1Molecules (Basel, Switzerland) · 2023Article
- 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
- Small Molecule Inhibitors of Protein Kinase D: Early Development, Current Approaches, and Future Directions.Journal of medicinal chemistry · 2023Review
- Article
- Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases.Biomolecules · 2021Review
- Small-Molecule Inhibitor Targeting Protein Kinase D: A Potential Therapeutic Strategy.Frontiers in oncology · 2021Review
- AlleleAnalyzer: a tool for personalized and allele-specific sgRNA design.Genome biology · 2019Article
- Protein Kinase D2 Modulates Cell Cycle By Stabilizing Aurora A Kinase at Centrosomes.Molecular cancer research : MCR · 2018Article
- Protein kinase D2: a versatile player in cancer biology.Oncogene · 2018Review
- Microtubule affinity-regulating kinases are potential druggable targets for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2017Review
- Protein kinase D signaling in cancer: A friend or foe?Biochimica et biophysica acta. Reviews on cancer · 2017Review
- Kinobead and Single-Shot LC-MS Profiling Identifies Selective PKD Inhibitors.Journal of proteome research · 2017Article
- Discovery of a potent protein kinase D inhibitor: insights in the binding mode of pyrazolo[3,4-MedChemComm · 2017Article
- Androgen suppresses protein kinase D1 expression through fibroblast growth factor receptor substrate 2 in prostate cancer cells.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The emergence of protein kinase D (PKD) as a potential therapeutic target for several diseases including cancer has triggered the search for potent, selective, and cell-permeable small molecule inhibitors. In this study, we describe the identification, in vitro characterization, structure-activity analysis, and biological evaluation of a novel PKD inhibitory scaffold exemplified by 1-naphthyl PP1 (1-NA-PP1). 1-NA-PP1 and IKK-16 were identified as pan-PKD inhibitors in a small-scale targeted kinase inhibitor library assay. Both screening hits inhibited PKD isoforms at about 100 nM and were ATP-competitive inhibitors. Analysis of several related kinases indicated that 1-NA-PP1 was highly selective for PKD as compared to IKK-16. SAR analysis showed that 1-NA-PP1 was considerably more potent and showed distinct substituent effects at the pyrazolopyrimidine core. 1-NA-PP1 was cell-active, and potently blocked prostate cancer cell proliferation by inducing G2/M arrest. It also potently blocked the migration and invasion of prostate cancer cells, demonstrating promising anticancer activities on multiple fronts. Overexpression of PKD1 or PKD3 almost completely reversed the growth arrest and the inhibition of tumor cell invasion caused by 1-NA-PP1, indicating that its anti-proliferative and anti-invasive activities were mediated through the inhibition of PKD. Interestingly, a 12-fold increase in sensitivity to 1-NA-PP1 could be achieved by engineering a gatekeeper mutation in the active site of PKD1, suggesting that 1-NA-PP1 could be paired with the analog-sensitive PKD1(M659G) for dissecting PKD-specific functions and signaling pathways in various biological systems.
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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.