ArticleBiochemical pharmacology2017
Dual activities of ritanserin and R59022 as DGKα inhibitors and serotonin receptor antagonists.
Article in Biochemical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 66 citations in OpenAlex.
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- Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
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- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- In Silico Identification and Characterization of Spiro[1,2,4]triazolo[1,5-Molecules (Basel, Switzerland) · 2025Article
- Repurposing serotonergic drugs for gastric cancer: induction of apoptosis in vitro.Molecular biology reports · 2025Article
- Article
- Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases.International journal of molecular sciences · 2024Review
- Diacylglycerol kinase is a keystone regulator of signaling relevant to the pathophysiology of asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.Science advances · 2023Article
- Discovery of Potent, Dual-Inhibitors of Diacylglycerol Kinases Alpha and Zeta Guided by Phenotypic Optimization.ACS medicinal chemistry letters · 2023Article
- Ritanserin suppresses acute myeloid leukemia by inhibiting DGKα to downregulate phospholipase D and the Jak-Stat/MAPK pathway.Discover oncology · 2023Article
- Role of Diacylglycerol Kinases in Acute Myeloid Leukemia.Biomedicines · 2023Article
- Predicting small molecule binding pockets on diacylglycerol kinases using chemoproteomics and AlphaFold.RSC chemical biology · 2023Article
- Targeting diacylglycerol kinase α impairs lung tumorigenesis by inhibiting cyclin D3.Thoracic cancer · 2023Article
- A Drosophila chemical screen reveals synergistic effect of MEK and DGKα inhibition in Ras-driven cancer.Disease models & mechanisms · 2023Article
- Small molecule inhibitors for cancer immunotherapy and associated biomarkers - the current status.Frontiers in immunology · 2023Review
- Dysregulated lipid metabolism in lymphangioleiomyomatosis pathogenesis as a paradigm of chronic lung diseases.Frontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Diacylglycerol kinase alpha (DGKα) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA). Recently, DGKα was identified as a therapeutic target in various cancers, as well as in immunotherapy. Application of small-molecule DGK inhibitors, R59022 and R59949, induces cancer cell death in vitro and in vivo. The pharmacokinetics of these compounds in mice, however, are poor. Thus, there is a need to discover additional DGK inhibitors not only to validate these enzymes as targets in oncology, but also to achieve a better understanding of their biology. In the present study, we investigate the activity of ritanserin, a compound structurally similar to R59022, against DGKα. Ritanserin, originally characterized as a serotonin (5-HT) receptor (5-HTR) antagonist, underwent clinical trials as a potential medicine for the treatment of schizophrenia and substance dependence. We document herein that ritanserin attenuates DGKα kinase activity while increasing the enzyme's affinity for ATP in vitro. In addition, R59022 and ritanserin function as DGKα inhibitors in cultured cells and activate protein kinase C (PKC). While recognizing that ritanserin attenuates DGK activity, we also find that R59022 and R59949 are 5-HTR antagonists. In conclusion, ritanserin, R59022 and R59949 are combined pharmacological inhibitors of DGKα and 5-HTRs in vitro.
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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 Socratic graph.