ArticleCell chemical biology2018
Targeting Pim Kinases and DAPK3 to Control Hypertension.
Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Multi-Modal Kinome Profiling Discovers Mesenchymal-Like Polarity Networks that Underly Directed Hepatocellular Carcinoma Cell Migration.bioRxiv : the preprint server for biology · 2026Article
- The Research Progress in Targeted Therapy for Hypertension via Heat Shock Proteins.International journal of molecular sciences · 2026Review
- Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.Experimental hematology & oncology · 2026Article
- An Inhibitor of Death-Associated Protein Kinase 3 (DAPK3) Disrupts Hippo Signaling and Intestinal Epithelial Regeneration in Murine DSS-Induced Colitis.Digestive diseases and sciences · 2026Article
- Zipper-interacting protein kinase mediates neuronal cell death and cognitive dysfunction in traumatic brain injury via regulating DEDD.Cell death & disease · 2025Article
- Organ-specific off-target effects of Pim/ZIP kinase inhibitors suggest lack of contractile Pim kinase activity in prostate, bladder, and vascular smooth muscle.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Pim Kinases: Important Regulators of Cardiovascular Disease.International journal of molecular sciences · 2023Review
- Death-associated protein kinase 3 regulates the myogenic reactivity of cerebral arteries.Experimental physiology · 2023Article
- p90RSK2, a new MLCK mediates contractility in myosin light chain kinase null smooth muscle.Frontiers in physiology · 2023Article
- The Role of PIM Kinases in Pediatric Solid Tumors.Cancers · 2022Review
- New insights into the characteristics of DRAK2 and its role in apoptosis: From molecular mechanisms to clinically applied potential.Frontiers in pharmacology · 2022Review
- C─H⋯O hydrogen bonds in kinase-inhibitor interfaces.IUBMB life · 2020Article
- RSK2 contributes to myogenic vasoconstriction of resistance arteries by activating smooth muscle myosin and the NaScience signaling · 2018Article
- Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated Protein Kinase-Related Signals.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
Sustained vascular smooth muscle hypercontractility promotes hypertension and cardiovascular disease. The etiology of hypercontractility is not completely understood. New therapeutic targets remain vitally important for drug discovery. Here we report that Pim kinases, in combination with DAPK3, regulate contractility and control hypertension. Using a co-crystal structure of lead molecule (HS38) in complex with DAPK3, a dual Pim/DAPK3 inhibitor (HS56) and selective DAPK3 inhibitors (HS94 and HS148) were developed to provide mechanistic insight into the polypharmacology of hypertension. In vitro and ex vivo studies indicated that Pim kinases directly phosphorylate smooth muscle targets and that Pim/DAPK3 inhibition, unlike selective DAPK3 inhibition, significantly reduces contractility. In vivo, HS56 decreased blood pressure in spontaneously hypertensive mice in a dose-dependent manner without affecting heart rate. These findings suggest including Pim kinase inhibition within a multi-target engagement strategy for hypertension management. HS56 represents a significant step in the development of molecularly targeted antihypertensive medications.
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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.