ReviewDrug discovery today2020
PDE5 and PDE10 inhibition activates cGMP/PKG signaling to block Wnt/β-catenin transcription, cancer cell growth, and tumor immunity.
Review in Drug discovery today, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Pharmacological mechanism and therapeutic efficacy of Icariside II in the treatment of acute ischemic stroke: a systematic review and network pharmacological analysis.BMC complementary medicine and therapies · 2022Pooled it
- Nitric oxide dependent metabolic and genetic dysregulation in metastatic triple-negative breast cancer.The Journal of biological chemistry · 2026Article
- TPx Protein ofPathogens (Basel, Switzerland) · 2026Article
- Machine learning-based determination of sex-related bladder cancer biomarkers.Frontiers in bioinformatics · 2026Article
- Clinical and Functional Characterization of PDE1A as a Wnt/Oncology research · 2026Article
- Sulfur and Selenium Modifications at Phosphorus Atom in Nucleoside Monophosphates, Activity and Potential Applications.Current medicinal chemistry · 2026Review
- Machine-learning-based determination of sex-related bladder cancer biomarkers.bioRxiv : the preprint server for biology · 2025Article
- TRIM32 promotes tumor immune evasion and impedes Anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer.Journal of translational medicine · 2025Article
- Article
- NSAID-encapsulated nanoparticles as a targeted therapeutic platform for modulating chronic inflammation and inhibiting cancer progression: a review.Inflammopharmacology · 2025Review
- Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription.Communications biology · 2025Article
- Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.Anti-cancer agents in medicinal chemistry · 2025Article
- Sodium arsenite-induced DNA methylation alterations exacerbated by p53 knockout in MCF7 cells.Heliyon · 2024Article
- Pan-cancer bioinformatics analysis of hepatic leukemia factor and further validation in colorectal cancer.Translational cancer research · 2024Article
- Phosphodiesterase Inhibition to Sensitize Non-Small-Cell Lung Cancer to Pemetrexed: A Double-Edged Strategy.Cancers · 2024Article
- 8-Br-cGMP suppresses tumor progression through EGFR/PLC γ1 pathway in epithelial ovarian cancer.Molecular biology reports · 2024Article
- HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients.Frontiers in immunology · 2024Article
- Analysis of the potential biological significance of glycosylation in triple-negative breast cancer on patient prognosis.American journal of translational research · 2024Article
- Lymph node metastasis-related lncRNA GAS6-AS1 facilitates the progression of esophageal squamous cell carcinoma.Journal of gastrointestinal oncology · 2023Article
- Pharmacological Evidence ThatMolecules (Basel, Switzerland) · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Although numerous reports conclude that nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer activity, this common drug class is not recommended for long-term use because of potentially fatal toxicities from cyclooxygenase (COX) inhibition. Studies suggest the mechanism responsible for the anticancer activity of the NSAID sulindac is unrelated to COX inhibition but instead involves an off-target, phosphodiesterase (PDE). Thus, it might be feasible develop safer and more efficacious drugs for cancer indications by targeting PDE5 and PDE10, which are overexpressed in various tumors and essential for cancer cell growth. In this review, we describe the rationale for using the sulindac scaffold to design-out COX inhibitory activity, while improving potency and selectivity to inhibit PDE5 and PDE10 that activate cGMP/PKG signaling to suppress Wnt/β-catenin transcription, cancer cell growth, and tumor immunity.
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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.