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Journal articles on the topic 'Pleiotropic prodrugs'

Author: Grafiati

Published: 21 December 2024

Last updated: 31 July 2025

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1

Li, Jiaqi. "Advances and applications of prodrug strategies in drug design." Journal of Food Science, Nutrition and Health 3, no. 1 (2024): 12–22. https://doi.org/10.54254/3029-0821/3/2024023.

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Of all the drugs launched on the market over the past decade, a substantial number of approved prodrugs have been significant, underscoring the importance of this prodrug to drug design. It is reported that 10% of all marketed drugs globally can be classified as prodrugs. The core goal of the prodrug strategy is to improve the undesirable properties of the drug molecule, including but not limited to insufficient solubility, low selectivity, poor chemical stability, poor taste, strong local irritation, significant pain, and possible systemic toxicity during metabolism in vivo. This review artic

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2

Toublet, François-Xavier, Cédric Lecoutey, Julien Lalut, et al. "Inhibiting Acetylcholinesterase to Activate Pleiotropic Prodrugs with Therapeutic Interest in Alzheimer’s Disease." Molecules 24, no. 15 (2019): 2786. http://dx.doi.org/10.3390/molecules24152786.

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Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease which is still poorly understood. The drugs currently used against AD, mainly acetylcholinesterase inhibitors (AChEI), are considered clinically insufficient and are responsible for deleterious side effects. AChE is, however, currently receiving renewed interest through the discovery of a chaperone role played in the pathogenesis of AD. But AChE could also serve as an activating protein for pleiotropic prodrugs. Indeed, inhibiting central AChE with brain-penetrating designed carbamates which are able to covalently bind to t

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Chirumbolo, Salvatore, Geir Bjørklund, Roman Lysiuk, Antonio Vella, Larysa Lenchyk, and Taras Upyr. "Targeting Cancer with Phytochemicals via Their Fine Tuning of the Cell Survival Signaling Pathways." International Journal of Molecular Sciences 19, no. 11 (2018): 3568. http://dx.doi.org/10.3390/ijms19113568.

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The role of phytochemicals as potential prodrugs or therapeutic substances against tumors has come in the spotlight in the very recent years, thanks to the huge mass of encouraging and promising results of the in vitro activity of many phenolic compounds from plant raw extracts against many cancer cell lines. Little but important evidence can be retrieved from the clinical and nutritional scientific literature, where flavonoids are investigated as major pro-apoptotic and anti-metastatic compounds. However, the actual role of these compounds in cancer is still far to be fully elucidated. Many o

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Campos-Salinas, Jenny, Margarita Barriga, and Mario Delgado. "Therapeutic Effect of a Latent Form of Cortistatin in Experimental Inflammatory and Fibrotic Disorders." Pharmaceutics 14, no. 12 (2022): 2785. http://dx.doi.org/10.3390/pharmaceutics14122785.

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Cortistatin is a cyclic neuropeptide that recently emerged as an attractive therapeutic factor for treating inflammatory, autoimmune, fibrotic, and pain disorders. Despite of its efficiency and apparent safety in experimental preclinical models, its short half-life in body fluids and its potential pleiotropic effects, due to its promiscuity for several receptors expressed in various cells and tissues, represent two major drawbacks for the clinical translation of cortistatin-based therapies. Therefore, the design of new strategies focused on increasing the stability, bioavailability, and target

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5

Toublet, François-Xavier, Julien Lalut, Bérénice Hatat, et al. "Pleiotropic prodrugs: Design of a dual butyrylcholinesterase inhibitor and 5-HT6 receptor antagonist with therapeutic interest in Alzheimer’s disease." European Journal of Medicinal Chemistry 210 (January 2021): 113059. http://dx.doi.org/10.1016/j.ejmech.2020.113059.

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6

Leitsch, David. "A review on metronidazole: an old warhorse in antimicrobial chemotherapy." Parasitology 146, no. 9 (2017): 1167–78. http://dx.doi.org/10.1017/s0031182017002025.

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AbstractThe 5-nitroimidazole drug metronidazole has remained the drug of choice in the treatment of anaerobic infections, parasitic as well as bacterial, ever since its development in 1959. In contrast to most other antimicrobials, it has a pleiotropic mode of action and reacts with a large number of molecules. Importantly, metronidazole, which is strictly speaking a prodrug, needs to be reduced at its nitro group in order to become toxic. Reduction of metronidazole, however, only takes place under very low concentrations of oxygen, explaining why metronidazole is exclusively toxic to microaer

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7

Bettendorff, Lucien. "Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases." International Journal of Molecular Sciences 24, no. 14 (2023): 11296. http://dx.doi.org/10.3390/ijms241411296.

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Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has no known adverse effects and improves cognitive outcomes in patients with mild Alzheimer’s disease. In cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent o

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8

Nirschl, Christopher J., Pam Alderhold, Heather R. Brodkin, et al. "Abstract 2055: WTX-330 is a conditionally activated IL-12 prodrug that fundamentally reprograms tumor infiltrating CD8+ T cells and drives tumor regression." Cancer Research 82, no. 12_Supplement (2022): 2055. http://dx.doi.org/10.1158/1538-7445.am2022-2055.

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Abstract Immune checkpoint inhibition (ICI) has established immunotherapy as the first line of treatment in a subset of cancers. However, there are still many patients and cancer types where ICI is not effective, representing a significant unmet clinical need for novel immunotherapies to expand the clinical options for patients. Interleukin 12 (IL-12) is a pleiotropic cytokine that drives naïve T cells towards a TH1 phenotype, activates NK cells and cytotoxic T cells, and strongly induces the expression of IFNγ by multiple cell types, making it an attractive pro-inflammatory cytokine for cance

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9

Su, Qingtai, Stephen Gutowski, Austin Burcham, et al. "Abstract LB438: Preclinical characterization of ONM-412, an ultra-pH sensitive nanoparticle encapsulated IL-12 fusion protein." Cancer Research 84, no. 7_Supplement (2024): LB438. http://dx.doi.org/10.1158/1538-7445.am2024-lb438.

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Abstract Background: Interleukin-12 is a potent pleiotropic cytokine, but its clinical translation has been hindered by toxicities. To deliver IL-12 to tumors with high spatial and temporal precision while minimizing off-tumor effects, we have developed an ultra-pH sensitive nanoparticle platform - ON-BOARD - that shields payloads from systemic exposure and targets solid tumors by responding to tumor acidity. Herein, we report the preclinical efficacy and safety characterization of ONM-412, an ON-BOARD nanoparticle encapsulated IL-12Fc fusion protein, and muONM-412, an encapsulated murine IL-1

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10

Meden, Anže, Neža Žnidaršič, Damijan Knez, et al. "Pleiotropic prodrugs for both symptomatic and disease-modifying treatment of Alzheimer’s disease." Acta Pharmaceutica Sinica B, July 2025. https://doi.org/10.1016/j.apsb.2025.07.005.

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11

"Vitamin-D-Hormon-Prodrug Alfacalcidol - Die pleiotrope Therapieoption bei renaler Osteopathie." Dialyse aktuell 12, no. 08 (2008): 513. http://dx.doi.org/10.1055/s-0028-1104656.

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12

Zhang, Bingchen, Yuehua Wang, Shengtao Wang, et al. "Precise RNA Editing: Cascade Self‐Uncloaking Dual‐Prodrug Nanoassemblies Based on CRISPR/Cas13a for Pleiotropic Immunotherapy of PD‐L1‐Resistant Colorectal Cancer." Advanced Functional Materials, September 3, 2023. http://dx.doi.org/10.1002/adfm.202305630.

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AbstractCRISPR/Cas13a is a powerful genome editing system for RNA knockdown that holds enormous potential for cancer treatment by targeting currently undruggable oncogenes or immune checkpoints. However, the precise intratumoral activation of CRISPR/Cas13a to maximize the therapeutic efficiency while guaranteeing biosafety remains a daunting challenge. Here, a cascade self‐uncloaking nanoassembly (SRC) based on a dual‐prodrug comprising SN38 and Cas13a/RNP is developed, and the external encapsulation is performed by coating with a ROS‐responsive probe, which is stimulated by the tumor microenv

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13

Zhao, Fangshi, Xiaoyi Wang, Wei Zhu, et al. "Low-dose pleiotropic radiosensitive nanoformulations for three-pronged radiochemotherapy of hypoxic brain glioblastoma under BOLD/DWI monitoring." Cancer Nanotechnology 14, no. 1 (2023). http://dx.doi.org/10.1186/s12645-023-00159-w.

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Abstract Background Hypoxia-mediated radioresistance is the main obstacle to the successful treatment of glioblastoma (GBM). Enhancing hypoxic radiosensitivity and alleviating tumor hypoxia are both effective means to improve therapeutic efficacy, and the combination of the two is highly desirable and meaningful. Results Herein, we construct a low-dose pleiotropic radiosensitive nanoformulation consisting of a high-Z atomic nanocrystal core and mesoporous silica shell, surface-modified with angiopep-2 (ANG) peptide and loaded with nitric oxide (NO) donor and hypoxia-activated prodrug (AQ4N). B

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14

Germann, Ryan. "In-Vitro Effect of Statins on Enterococcus Faecalis." Journal of Dental Health and Oral Research, January 29, 2024, 1–6. http://dx.doi.org/10.46889/jdhor.2024.5102.

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Objective: The aim of this study was to assess the in-vitro efficacy of statin medications on putative Enterococcus faecaelis, as determined by minimum inhibitory concentration. Methods: Enterococcus faecalis 47077 was grown in the presence of simvastatin lactone (prodrug), simvastatin carboxylate (active metabolite), rosuvastatin, pravastatin and fluvastatin. Minimum Inhibitory Concentrations (MICs) were determined by serial broth dilution assays and bacteriostatic activity by observing the effect of statin on growth curves. Results: MICs against E. faecalis were simvastatin lactone (26.1 μg/

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15

Faris, Pawan, Sharon Negri, Delia Faris, Francesca Scolari, Daniela Montagna, and Francesco Moccia. "Hydrogen Sulfide (H2S): As A Potent Modulator And Therapeutic Prodrug In Cancer." Current Medicinal Chemistry 30 (January 26, 2023). http://dx.doi.org/10.2174/0929867330666230126100638.

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Abstract: Hydrogen sulfide (H2S) is an endogenous gaseous molecule present in all living organisms and has been traditionally studied for its toxicity. Interestingly, increased understanding of H2S effects in organ physiology has recently shown its relevance as a signalling molecule, with potentially important implications in variety of clinical disorders, including cancer. H2S is primarily produced in mammalian cells under various enzymatic pathways. A developing focus of H2S is a blooming hotspot that studies chemical, biological mechanisms, and therapeutic effects of H2S. Herein, we describ

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16

Gebremariam, Teclegiorgis, Sondus Alkhazraji, Abdullah Alqarihi, et al. "Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus arrhizus." Antimicrobial Agents and Chemotherapy 64, no. 6 (2020). http://dx.doi.org/10.1128/aac.00178-20.

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ABSTRACT Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, a protein involved in an early step in the conserved glycosylphosphotidyl inositol (GPI) posttranslational modification pathway of surface proteins in eukaryotic cells. Inhibition of fungal inositol acylation by MGX results in pleiotropic effects, including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have in vitro activity against some

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