Journal Description
Future Pharmacology
Future Pharmacology
is an international, peer-reviewed, open access journal on pharmacology, drug discovery, and therapeutics published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), EBSCO, and other databases.
- Journal Rank: JCR - Q2 (Pharmacology and Pharmacy)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 21.8 days after submission; acceptance to publication is undertaken in 4.7 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- Future Pharmacology is a companion journal of Pharmaceutics.
- Journal Clusters-Pharmaceutical Science: Scientia Pharmaceutica, Pharmaceuticals, Pharmaceutics, Pharmacy, Future Pharmacology, Pharmacoepidemiology, Drugs and Drug Candidates and Journal of Pharmaceutical and BioTech Industry.
Impact Factor:
2.7 (2024);
5-Year Impact Factor:
2.7 (2024)
Latest Articles
The Effect of Co-Administration of Levetiracetam or Brivaracetam with Ethanol on the Associative Learning and Anxiety Level of Rats
Future Pharmacol. 2025, 5(3), 45; https://doi.org/10.3390/futurepharmacol5030045 - 21 Aug 2025
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Background: Ethanol intake leads to cognitive deficits. Recent research demonstrated that a dysregulation of synaptic vesicle glycoprotein 2A (SV2A) expression seems to be linked to anxiety and memory disorders. Levetiracetam and brivaracetam are two antiseizure drugs that affect the SV2A protein. This study
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Background: Ethanol intake leads to cognitive deficits. Recent research demonstrated that a dysregulation of synaptic vesicle glycoprotein 2A (SV2A) expression seems to be linked to anxiety and memory disorders. Levetiracetam and brivaracetam are two antiseizure drugs that affect the SV2A protein. This study aimed to assess the impact of these drugs on associative learning and anxiety-like behaviors in ethanol-treated rats. Methods: Adult male Wistar rats (n = 64) were given brivaracetam or levetiracetam via i.g. for three weeks at doses of 300 mg/kg or 6 mg/kg, respectively. Ethanol was administered as a 20% solution twice a day, via i.g., at a morning dose of 1.5 g/kg b.w. and an afternoon dose of 3.5 g/kg b.w. Additionally, 5% ethanol was available ad libitum between 4:00 p.m. and 8:00 a.m. Associative learning was evaluated using the passive avoidance test during the alcohol administration period, as well as the contextual fear conditioning and cued fear conditioning tests during the withdrawal period. The level of anxiety was determined using the elevated plus maze test in withdrawal rats. Results: Ethanol consumption resulted in impaired associative memory, and its withdrawal was linked to increased anxiety levels. Levetiracetam enhanced memory performance in the passive avoidance test, but brivaracetam disturbed memory associated with unpleasant stimuli in the contextual fear conditioning. Additionally, withdrawal-induced disturbance of locomotor activity persisted, particularly in animals receiving levetiracetam in the elevated plus maze. Conclusions: Levetiracetam appears to provide certain beneficial effects, whereas brivaracetam may worsen memory disturbances in rats.
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Open AccessReview
Antimicrobial Efficacy of Curcumin Nanoparticles Against Aquatic Bacterial Pathogens
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Edith Dube and Grace Emily Okuthe
Future Pharmacol. 2025, 5(3), 44; https://doi.org/10.3390/futurepharmacol5030044 - 19 Aug 2025
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Bacterial diseases are a major constraint to aquaculture productivity, driving extensive antibiotic use and raising concerns over antimicrobial resistance, environmental contamination, and food safety. Curcumin, a polyphenolic compound from Curcuma longa, exhibits broad-spectrum antimicrobial and immunomodulatory activities but is limited by poor
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Bacterial diseases are a major constraint to aquaculture productivity, driving extensive antibiotic use and raising concerns over antimicrobial resistance, environmental contamination, and food safety. Curcumin, a polyphenolic compound from Curcuma longa, exhibits broad-spectrum antimicrobial and immunomodulatory activities but is limited by poor water solubility, instability, and low bioavailability. This review was conducted through a literature search of Scopus, PubMed, Web of Science, and Google Scholar using targeted keywords, including curcumin nanoparticles, antibacterial, aquatic pathogens, nanotechnology, synthesis, and disease control. Titles and abstracts were screened for relevance, followed by full-text evaluation of selected studies. Key findings were critically analyzed and incorporated into the review. Findings from the literature indicate that curcumin nanoparticles, synthesized via milling, anti-solvent precipitation, ionic gelation, emulsification, spray drying, and metal/polymer nanocomposite formation, exhibit enhanced antibacterial activity against aquatic pathogens, including Aeromonas hydrophila, Vibrio parahaemolyticus, Escherichia coli, and Staphylococcus aureus. Optimally engineered curcumin nanoparticles (<100 nm, being mostly spherical, highly negatively charged) can penetrate bacterial membranes, disrupt biofilms, lower minimum inhibitory concentrations, and improve in vivo fish survival. Practical applications include dietary supplementation to boost fish immunity and growth, water disinfection to reduce pathogen loads, immersion therapy for external infections, and antimicrobial coatings for aquaculture equipment and surfaces, resulting in reduced infections and outbreaks, reduced mortality, improved water quality, and decreased antibiotic dependence. In conclusion, curcumin nanoparticles and curcumin-based nanocomposites present a versatile, eco-friendly approach to sustainable aquaculture disease management. However, further field-scale validation, safety assessment, and cost-effective production methods are necessary to enable commercial adoption.
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Open AccessReview
Assessing the Pharmacological and Pharmacogenomic Data of PD-1/PD-L1 Inhibitors to Enhance Cancer Immunotherapy Outcomes in the Clinical Setting
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Damianos-Ioannis Zervanos, Eleftheria Galatou, Androulla N. Miliotou, Nikoleta F. Theodoroula, Nikolaos Grigoriadis and Ioannis S. Vizirianakis
Future Pharmacol. 2025, 5(3), 43; https://doi.org/10.3390/futurepharmacol5030043 - 10 Aug 2025
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Background/Objectives: Advances in understanding immune checkpoint pathways and tumor immune biology have enabled the development of immune checkpoint inhibitors (ICIs), particularly targeting the PD-1/PD-L1 axis, which has transformed cancer immunotherapy. While they have shown remarkable success in various cancer types, including melanoma,
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Background/Objectives: Advances in understanding immune checkpoint pathways and tumor immune biology have enabled the development of immune checkpoint inhibitors (ICIs), particularly targeting the PD-1/PD-L1 axis, which has transformed cancer immunotherapy. While they have shown remarkable success in various cancer types, including melanoma, non-small cell lung cancer, and gastrointestinal malignancies, variability in patient response, immune-related adverse events (irAEs), and resistance mechanisms remain significant. This review aims to evaluate clinical pharmacology, mechanisms of action, resistance pathways, and pharmacogenomic influences shaping interindividual responses to ICIs. Methods: This comprehensive review synthesizes current literature on FDA-approved ICIs, exploring their clinical use, underlying biological mechanisms, and emerging pharmacogenomic data. It also assesses key biomarkers such as tumor mutational burden (TMB), microsatellite instability (MSI), HLA diversity, and epigenetic factors influencing ICI efficacy and safety. Results: We outline key mechanisms contributing to ICI resistance, including T cell dysfunction, altered antigen presentation, and immunosuppressive tumor microenvironment components. Furthermore, we highlight promising pharmacogenomic findings, including single-nucleotide polymorphisms (SNPs) in PD-1/PD-L1 and immune-regulatory genes, offering predictive and prognostic utility. Variability in PD-L1 expression and the role of epigenetic modifications are also addressed as challenges in treatment optimization. Conclusions: Interindividual variability in ICI response underscores the need for biomarker-driven strategies. By integrating pharmacogenomic insights with clinical pharmacology, future approaches may support more personalized and effective use of ICIs. Combination therapies and novel modalities hold promise for overcoming resistance, enhancing therapeutic efficacy, and enabling precision oncology.
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Open AccessReview
Future Pharmacotherapy for Bipolar Disorders: Emerging Trends and Personalized Approaches
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Giuseppe Marano, Francesco Maria Lisci, Gianluca Boggio, Ester Maria Marzo, Francesca Abate, Greta Sfratta, Gianandrea Traversi, Osvaldo Mazza, Roberto Pola, Gabriele Sani, Eleonora Gaetani and Marianna Mazza
Future Pharmacol. 2025, 5(3), 42; https://doi.org/10.3390/futurepharmacol5030042 - 4 Aug 2025
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Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse
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Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry.
Full article
(This article belongs to the Special Issue Transdiagnostic Psychopharmacology: Bridging Mechanisms Across Mental Disorders)
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Open AccessReview
Oxygen-Generating Metal Peroxide Particles for Cancer Therapy, Diagnosis, and Theranostics
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Adnan Memić and Turdimuhammad Abdullah
Future Pharmacol. 2025, 5(3), 41; https://doi.org/10.3390/futurepharmacol5030041 - 30 Jul 2025
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Theranostic materials, which combine therapeutic and diagnostic capabilities, represent a promising advancement in cancer treatment by improving both the precision and personalization of therapies. Recently, metal peroxides (MePOs) have attracted significant interest from researchers for their potential use in both cancer diagnosis and
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Theranostic materials, which combine therapeutic and diagnostic capabilities, represent a promising advancement in cancer treatment by improving both the precision and personalization of therapies. Recently, metal peroxides (MePOs) have attracted significant interest from researchers for their potential use in both cancer diagnosis and therapy. This review provides an overview of recent developments in the application of MePOs for innovative cancer treatment strategies. The unique properties of MePOs, such as oxygen generation, are highlighted for their potential to improve therapeutic outcomes, especially in hypoxic tumor microenvironments. Initially, methods for MePO synthesis are briefly discussed, including hydrolyzation–precipitation, reversed-phase microemulsion, and sonochemical techniques, emphasizing the role of surfactants in regulating the particle size and enhancing bioactivity. Next, we discuss the main therapeutic approaches where MePOs have shown promise. These applications include chemotherapy, photodynamic therapy (PDT), immunotherapy, and radiation therapy. Overall, we focus on integrating MePOs into theranostic platforms to enhance cancer treatment and enable diagnostic imaging for improved clinical outcomes. Finally, we discuss potential future research directions that could lead to clinical translation and the development of advanced medicines.
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Open AccessReview
Old and New Analgesic Acetaminophen: Pharmacological Mechanisms Compared with Non-Steroidal Anti-Inflammatory Drugs
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Hironori Tsuchiya and Maki Mizogami
Future Pharmacol. 2025, 5(3), 40; https://doi.org/10.3390/futurepharmacol5030040 - 22 Jul 2025
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Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during
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Although it is more than a century since it was first marketed, acetaminophen remains one of the most popular analgesic agents. In addition, acetaminophen has recently been applied to multimodal analgesia in combination with non-steroidal anti-inflammatory drugs, and its consumption significantly increased during the pandemic of coronavirus disease 2019 as well as diclofenac and ibuprofen. However, the detailed mode of analgesic action of acetaminophen is still unclear. In the present study, we comprehensively discuss conventional, recognized, and postulated mechanisms of analgesic acetaminophen and highlight the current mechanistic concepts while comparing with diclofenac and ibuprofen. Acetaminophen inhibits cyclooxygenase with selectivity for cyclooxygenase-2, which is higher than that of ibuprofen but lower than that of diclofenac. In contrast to diclofenac and ibuprofen, however, anti-inflammatory effects of acetaminophen depend on the extracellular conditions of inflamed tissues. Since the discovery of cyclooxygenase-3 in the canine brain, acetaminophen had been hypothesized to inhibit such a cyclooxygenase-1 variant selectively. However, this hypothesis was abandoned because cyclooxygenase-3 was revealed not to be physiologically and clinically relevant to humans. Recent studies suggest that acetaminophen is deacetylated to 4-aminophenol in the liver and after crossing the blood–brain barrier, it is metabolically converted into N-(4-hydroxyphenyl)arachidonoylamide. This metabolite exhibits bioactivities by targeting transient receptor potential vanilloid 1 channel, cannabinoid receptor 1, Cav3.2 calcium channel, anandamide, and cyclooxygenase, mediating acetaminophen analgesia. These targets may be partly associated with diclofenac and ibuprofen. The perspective of acetaminophen as a prodrug will be crucial for a future strategy to develop analgesics with higher tolerability and activity.
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Open AccessReview
Design of an Array to Evaluate Biomarkers of Response to Biological Treatments in Inflammatory Bowel Disease
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Andrea Rodríguez-Lopez, Eva González-Iglesias, Jesús Novalbos, Susana Almenara and Francisco Abad-Santos
Future Pharmacol. 2025, 5(3), 39; https://doi.org/10.3390/futurepharmacol5030039 - 14 Jul 2025
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Background: Inflammatory bowel disease (IBD) is defined as recurrent inflammatory bowel disorders, the most common of which are Crohn’s disease (CD) and ulcerative colitis (UC). Tumor necrosis factor inhibitors (anti-TNFs), primarily adalimumab (ADA), infliximab (IFX), ustekinumab (UST), and vedolizumab (VLZ), are used to
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Background: Inflammatory bowel disease (IBD) is defined as recurrent inflammatory bowel disorders, the most common of which are Crohn’s disease (CD) and ulcerative colitis (UC). Tumor necrosis factor inhibitors (anti-TNFs), primarily adalimumab (ADA), infliximab (IFX), ustekinumab (UST), and vedolizumab (VLZ), are used to treat moderate-to-severe cases of IBD in patients who either do not tolerate or fail to respond to conventional therapies. However, about one-third of patients are primary non-responders to these treatments, and an additional 30% lose response over time. Several studies have investigated the role of genetic variability in explaining these differences in treatment response among patients. The aim of this study was to design an array of 60 single-nucleotide variants (SNVs) to validate the biomarkers described in the literature in a population of more than 400 IBD patients treated with biological drugs. Method: The primary focus of this study was the most recent reviews published in PubMed, with all relevant SNVs selected for the array design. Subsequently, studies presenting original data on the association between variants and the response to biological treatment were identified. Results: A total of 55.9% of SNVs have been studied in CD, 18.6% have been in UC, and 25.4% have been studied in both pathologies. A total of 44.1% of SNVs have been observed to influence the response to IFX, 16.9% influence the response to ADA, and 37.3% influence the response to both IFX and ADA; however, only one study (1.7%) reported an influence on the response to UST and none reported an influence on the response to VLZ. Conclusions: An array comprising 38 genes and 59 SNVs has been designed to be used to validate biomarkers associated with responses to biologic drug treatments in IBD.
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Open AccessReview
Repurposing Terbutaline and Milrinone for Cancer Therapy: A Comprehensive Review
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Eduarda Ribeiro and Nuno Vale
Future Pharmacol. 2025, 5(3), 38; https://doi.org/10.3390/futurepharmacol5030038 - 11 Jul 2025
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Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies. Drug repurposing offers a cost-effective approach to cancer treatment by identifying new anticancer applications for existing drugs. Terbutaline, a β2-adrenergic receptor agonist, and Milrinone, a phosphodiesterase-3 inhibitor, are traditionally used as
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Cancer remains a leading cause of mortality worldwide, necessitating innovative therapeutic strategies. Drug repurposing offers a cost-effective approach to cancer treatment by identifying new anticancer applications for existing drugs. Terbutaline, a β2-adrenergic receptor agonist, and Milrinone, a phosphodiesterase-3 inhibitor, are traditionally used as positive inotropic agents but have shown potential anticancer effects. This review explores their mechanisms of action in cancer, focusing on their roles in modulating cyclic adenosine monophosphate (cAMP) levels, oxidative stress, and the tumor microenvironment. Terbutaline influences β2-adrenergic signaling, impacting cell proliferation, angiogenesis, and immune evasion. Milrinone, through PDE3 inhibition, elevates cAMP, promoting apoptosis and reducing tumor growth. Both agents exhibit anti-inflammatory and anti-angiogenic properties, suggesting their potential as adjuvant therapies in oncology. Despite promising preclinical data, clinical validation is required to confirm their efficacy and safety in cancer patients. This review highlights the therapeutic promise of repurposing Terbutaline and Milrinone, emphasizing the need for further research to optimize their application in cancer therapy.
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Open AccessReview
Genetic Markers Associated with Ferroptosis in Cardiovascular Diseases
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Brandon Fisher-Bautista, Gabriela Fonseca-Camarillo and Alfredo Cruz-Gregorio
Future Pharmacol. 2025, 5(3), 37; https://doi.org/10.3390/futurepharmacol5030037 - 11 Jul 2025
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Recently, a number of new genes (NFE2L2, HFE, HMOX, HIF-1α, ALOX5, GPX4, PTGS2, and IL-6) have been recognized as playing a role in ferroptosis and genetic predisposition to cardiovascular diseases (CVDs). Identifying these novel genes may facilitate the discovery of therapeutic
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Recently, a number of new genes (NFE2L2, HFE, HMOX, HIF-1α, ALOX5, GPX4, PTGS2, and IL-6) have been recognized as playing a role in ferroptosis and genetic predisposition to cardiovascular diseases (CVDs). Identifying these novel genes may facilitate the discovery of therapeutic agents and improve the clinical evaluation of phenotypes and prognoses in CVD patients. In the future, it will be crucial to develop genetic markers that correlate with clinical outcomes for individuals with CVDs. This review highlights recent developments in ferroptosis research while interpreting how genetic factors may contribute to the pathogenesis of CVDs. Understanding this relationship could be invaluable for predicting disease progression in individual patients, informing suitable medical interventions, and facilitating early diagnosis and treatment. Furthermore, we examine the possible uses of these disorders in diagnosis and the various treatment strategies, along with the associated challenges and existing limitations.
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Open AccessReview
Next-Generation Cancer Models for Drug Testing: Recent Advances in Immunocompetent Microphysiological Systems
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Marlene Große, Martin Burchardt and Pedro Caetano Pinto
Future Pharmacol. 2025, 5(3), 36; https://doi.org/10.3390/futurepharmacol5030036 - 7 Jul 2025
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The success of checkpoint inhibitors in improving cancer patient survival has demonstrated the therapeutic potential of immunotherapies. This advancement has reshaped oncology treatment and driven interest in harnessing immune modulation for a wider range of diseases. However, developing drugs that modulate immune activity
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The success of checkpoint inhibitors in improving cancer patient survival has demonstrated the therapeutic potential of immunotherapies. This advancement has reshaped oncology treatment and driven interest in harnessing immune modulation for a wider range of diseases. However, developing drugs that modulate immune activity presents unique challenges. A major limitation in preclinical research is the inefficiency of testing human-specific immune targets in animal models, which often fail to translate to clinical outcomes. Additionally, conventional in vitro systems lack immune reactivity due to their static and monocellular nature, limiting their predictive value. Advanced in vitro models can bridge this gap by offering increasingly relevant human physiology for testing drug efficacy and safety, along with absorption, distribution, metabolism, and excretion (ADME). In particular, immune-competent spheroids, organoids, and organs-on-a-chip (OoC) have emerged as promising tools. Although still in their infancy, these microphysiological systems (MPSs) have demonstrated the feasibility of replicating immune responses ex vivo, providing a new avenue for studying immune-targeting drugs with higher translational potential. In this review, we explore recent advances in immune-competent organoid and OoC models, highlighting their capabilities and limitations. We provide a perspective on their applications for cancer drug testing, discussing how these systems could refine preclinical immuno-oncology research and accelerate the development of next-generation immunotherapies.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessReview
Targeting Gram-Negative Bacterial Biofilm with Innovative Therapies: Communication Silencing Strategies
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Milka Malešević and Branko Jovčić
Future Pharmacol. 2025, 5(3), 35; https://doi.org/10.3390/futurepharmacol5030035 - 3 Jul 2025
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Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific
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Biofilm-associated infections caused by Gram-negative bacteria, especially multidrug-resistant strains, frequently occur in intensive care units and represent a major therapeutic challenge. The economic burden of biofilm-associated infections is considerable, making the search for new treatment approaches a focal point for policymakers and scientific funding bodies. Biofilm formation is regulated by quorum sensing (QS), a population density-dependent communication mechanism between cells mediated by small diffusible signaling molecules. QS modulates various intracellular processes, and some features of QS are common to all Gram-negative bacteria. While there are differences in the QS regulatory networks of different Gram-negative bacterial species, a common feature of most Gram-negative bacteria is the ability of N-acylhomoserine lactones (AHL) as inducers to diffuse across the bacterial membrane and interact with receptors located either in the cytoplasm or on the inner membrane. Targeting QS by inhibiting the synthesis, transport, or perception of signaling molecules using small molecules, quorum quenching enzymes, antibodies, combinatorial therapies, or nanoparticles is a promising strategy to combat virulence. In-depth knowledge of biofilm biology, antibiotic susceptibility, and penetration mechanisms, as well as a deep understanding of anti-QS agents, will contribute to the development of antimicrobial therapies to combat biofilm infections. Advancing antimicrobial therapies against biofilm infections requires a deep understanding of biofilm biology, antibiotic susceptibility, penetration mechanisms, and anti-QS strategies. This can be achieved through in vivo and clinical studies, supported by state-of-the-art tools such as machine learning and artificial intelligence.
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Open AccessReview
Tumor Microenvironment: An Emerging Landscape for Lung Cancer Therapy
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S. M. Sohag, Sharmin Nur Toma, Md. Al-Imran Imon, Maiweilan Maihemuti, Famim Ahmed, Mst. Afsana Mimi, Imran Mahmud and Md. Mahmudul Hasan
Future Pharmacol. 2025, 5(3), 34; https://doi.org/10.3390/futurepharmacol5030034 - 30 Jun 2025
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The tumor microenvironment (TME) is crucial for the onset, development, and resistance to treatment of lung cancer. The tumor microenvironment consisting of a complex array of immune cells, fibroblasts, endothelial cells, extracellular matrix elements, and signaling molecules, facilitates tumor growth and spread while
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The tumor microenvironment (TME) is crucial for the onset, development, and resistance to treatment of lung cancer. The tumor microenvironment consisting of a complex array of immune cells, fibroblasts, endothelial cells, extracellular matrix elements, and signaling molecules, facilitates tumor growth and spread while inhibiting the body’s antitumor immune response. In lung cancer, tumor-associated macrophages, cancer-associated fibroblasts, mast cells, and dendritic cells interact through cytokines, chemokines, growth factors, and matrix metalloproteinases to create an immunosuppressive and proangiogenic milieu. Hypoxic conditions within the TME further enhance cancer cell adaptability through hypoxia-inducible factors (HIFs), promoting epithelial–mesenchymal transition, immune evasion, and metastasis. Moreover, miRNAs have emerged as key regulators of gene expression within the TME, offering novel insights into tumor behavior and potential therapeutic targets. Targeting dynamic interactions within the TME, particularly through the modulation of immune responses, angiogenesis, and stromal remodeling, offers promising avenues for precision pharmacological approaches. This review covers the current understanding of the lung TME, highlighting its impact on cancer pathophysiology and treatment strategies. Understanding and therapeutically reprogramming the TME may pave the way for personalized and more effective interventions for lung cancer treatment.
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Open AccessArticle
A Single-Group, Open-Label Study on the Systemic Bioavailability, Safety, and Local Tolerability of a New L-Thyroxine/Escin Gel Formulation in Healthy Women
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Giovanni Gori, Ferdinando De Negri, Anna Fioravanti, Francesca De Feo, Catia Castiglioni and Elisabetta Fini
Future Pharmacol. 2025, 5(3), 33; https://doi.org/10.3390/futurepharmacol5030033 - 27 Jun 2025
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Objective: This study evaluated the systemic bioavailability of L-thyroxine (L-T4) in healthy women following repeated cutaneous application of a new gel formulation containing L-T4 and escin. Plasma concentrations of free triiodothyronine (FT3), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) were also assessed, along
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Objective: This study evaluated the systemic bioavailability of L-thyroxine (L-T4) in healthy women following repeated cutaneous application of a new gel formulation containing L-T4 and escin. Plasma concentrations of free triiodothyronine (FT3), reverse triiodothyronine (rT3), and thyroid-stimulating hormone (TSH) were also assessed, along with local and systemic tolerability. Methods: Thirty healthy women participated in a single-group, open-label trial. L-thyroxine gel was applied at 20 g/day for the first 2 days and 10 g/day for the following 26 days (equivalent to 20 mg/day and 10 mg/day of L-T4, respectively). Blood samples were collected at Baseline, 5 and 24 h after the first application, and on Days 14, 28 (End of Treatment, EOT), and 42 (End of Study, EOS). Tolerability and safety were monitored throughout. Results: Plasma FT4 concentrations remained stable throughout the study, with no clinically significant changes from Baseline (1.13 ± 0.15 ng/dL) to EOT (1.11 ± 0.13 ng/dL). FT3 and TSH levels also remained within physiological ranges, with only a transient, non-clinically relevant decrease observed 5 h after the first application. No changes in rT3 concentrations were detected at any time point. No serious adverse events were reported. Conclusions: This study confirms that repeated application of L-thyroxine/escin gel over 28 days (total exposure of 300 g) does not affect systemic thyroid hormone levels and is well tolerated in healthy women. These findings support the hypothesis that intact skin acts as an effective barrier to transdermal L-T4 absorption.
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Open AccessReview
Drug Target Validation in Polyamine Metabolism and Drug Discovery Advancements to Combat Tuberculosis
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Xolani H. Makhoba and Sergii Krysenko
Future Pharmacol. 2025, 5(3), 32; https://doi.org/10.3390/futurepharmacol5030032 - 25 Jun 2025
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Bacterial natural ecological niches are characterized by variations in the availability of nutrients, resulting in a complex metabolism. Their impressive ability to adapt to changeable nutrient conditions is possible through the utilization of large amounts of substrates. Recent discoveries in bacterial metabolism have
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Bacterial natural ecological niches are characterized by variations in the availability of nutrients, resulting in a complex metabolism. Their impressive ability to adapt to changeable nutrient conditions is possible through the utilization of large amounts of substrates. Recent discoveries in bacterial metabolism have suggested the importance of polyamine metabolism in bacteria, particularly in those of the order Actinomycetales, in enabling them to survive in their natural habitats. This makes such enzymes promising targets to inhibit their growth. Since the polyamine metabolisms of soil bacteria of the genus Streptomyces and the human pathogenic Mycobacteria are surprisingly similar, target-based drug development in Streptomyces and Mycobacterium spp. is an alternative approach to the classical search for antibiotics. The recent development of drugs to treat epidemic diseases like tuberculosis (TB) has gained attention due to the occurrence of multidrug-resistant strains. In addition, drug repurposing plays a crucial role in the treatment of various complex diseases, such as malaria. With that notion, the treatment of TB could also benefit from this approach. For example, molecular chaperones, proteins that help other proteins to fold properly, are found in almost all living organisms, including the causative agents of TB. Therefore, targeting these molecules could help in the treatment of TB. We aim to summarize our knowledge of the nitrogen and carbon metabolism of the two closely related actinobacterial genera, Streptomyces and Mycobacterium, and of the identification of new potential drug targets.
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Open AccessReview
Mirogabalin for Neuropathic Pain: A Review of Non-Opioid Pharmacotherapy with Insights from Japan
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Mizuho Sumitani, Takamichi Kogure, Hiroaki Abe, Rikuhei Tsuchida, Reo Inoue and Masahiko Sumitani
Future Pharmacol. 2025, 5(3), 31; https://doi.org/10.3390/futurepharmacol5030031 - 25 Jun 2025
Abstract
Background and Aim: Neuropathic pain leads to a significant deterioration in health-related quality of life (HRQOL). Treating neuromusculoskeletal pain is especially important to prevent and improve physical frailty and the locomotive syndrome. Varied pharmacotherapies could be applicable for neuropathic pain patients, but evidence
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Background and Aim: Neuropathic pain leads to a significant deterioration in health-related quality of life (HRQOL). Treating neuromusculoskeletal pain is especially important to prevent and improve physical frailty and the locomotive syndrome. Varied pharmacotherapies could be applicable for neuropathic pain patients, but evidence has been limited for a wide range of neuropathic pain conditions with different etiologies. The aim of this review was to highlight mirogabalin, a novel calcium channel α2δ ligand which was first approved in Japan, and which is effective for various types of neuropathic pain diseases. Methods: We conducted a narrative review of the recent evidence that mirogabalin has significant analgesic potency for varied types of neuropathic pain conditions. Futher, this review highlighted specific advantages over other calcium channel ligands. Results: Analgesic potency of mirogabalin could cover peripheral neuropathic pain conditions including post-herpetic neuralgia, diabetic peripheral neuropathy, cauda equina syndrome caused by lumbar spinal stenosis, radiculopathy caused by cervical spondylosis, and also central neuropathic pain conditions like spinal cord injury. Mirogabalin consistently demonstrated daytime sleepiness and dizziness as adverse effects, but most of these were mild. Conclusions: Mirogabalin is recommended as the first-line drug against most molecular mechanisms that cause neuropathic pain regardless of whether they have a peripheral or central origin. Mirogabalin demonstrates relatively less daytime sleepiness, making it age-friendly in the current global situation where population aging is accelerated. Considering the epidemic of ‘opiophobia’ in Japan and other countries, pharmacotherapy using mirogabalin could treat neuropathic pain associated with cancer and its treatment (e.g., chemotherapy-induced peripheral neuropathy), as well as non-cancer etiologies worldwide.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessReview
Individualized Management of Osteoarthritis: The Role of Pharmacogenomics to Optimize Pain Therapy
by
Isabella M. Sturgeon and Youssef M. Roman
Future Pharmacol. 2025, 5(2), 30; https://doi.org/10.3390/futurepharmacol5020030 - 13 Jun 2025
Abstract
Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying
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Osteoarthritis (OA) is a multifactorial, degenerative joint disease that significantly impairs mobility and quality of life, especially among older adults. The growing aging population and increasing obesity rates are expected to increase the incidence and prevalence of OA. In the absence of Disease-Modifying Antirheumatic Drugs (DMARDs) for OA, current treatment strategies largely focus on symptom relief rather than disease modification. These symptomatic treatments often fail to account for the substantial inter-individual variability in drug response. Pharmacogenomics (PGx), the study of how genetic variation influences drug response, offers a promising approach to personalize OA therapy. This review explores the clinical and pharmacogenomic considerations of commonly used OA medications—acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), duloxetine, and tramadol—focusing on gene–drug interactions that influence efficacy, safety, and metabolism. Evidence-based recommendations from the Clinical Pharmacogenetics Implementation Consortium guidelines are discussed, where applicable, to highlight actionable genetic variants in very important pharmacogenes such as CYP2D6, CYP2C9, and other important drug-metabolizing encoding genes such as CYP2E1 and UGT1A6. While PGx data are not currently embedded in OA clinical treatment guidelines, their integration into clinical practice may enhance therapeutic outcomes and minimize adverse drug events. This review underscores the potential of PGx as a clinical tool in OA pain management, paving the way toward truly personalized medicine.
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(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2025)
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Open AccessReview
The Pharmacological Potential of Algal Polysaccharides in Food Applications and Chronic Disease Management
by
Xue Wu, Yuxin Guo, Congjie Dai and Chao Zhao
Future Pharmacol. 2025, 5(2), 29; https://doi.org/10.3390/futurepharmacol5020029 - 13 Jun 2025
Cited by 1
Abstract
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Algal polysaccharides are a kind of bioactive compound with diverse pharmacological applications, yet their structure–activity relationships and therapeutic potential in chronic disease management remain systematically underexplored. This review comprehensively analyzes the structural characteristics of brown, red, and green algal polysaccharides, revealing how specific
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Algal polysaccharides are a kind of bioactive compound with diverse pharmacological applications, yet their structure–activity relationships and therapeutic potential in chronic disease management remain systematically underexplored. This review comprehensively analyzes the structural characteristics of brown, red, and green algal polysaccharides, revealing how specific structural features—such as glycosidic linkage patterns and sulfate group positioning—dictate their biological activities. We also demonstrated their multifaceted roles in diabetes, cancer, and cardiovascular diseases through distinct mechanisms, including gut microbiota modulation via short-chain fatty acid production, antioxidant enzyme activation, and targeted inhibition of pathological signaling pathways like mTOR and JAK-STAT3. The work further evaluates extraction methodologies, highlighting the advantages of emerging techniques such as enzyme-assisted and ultrasonic extraction for preserving bioactive integrity. By integrating fundamental research with practical applications in functional foods, this synthesis provides critical insights for harnessing algal polysaccharides in precision nutrition and sustainable biomedicine, while identifying key challenges in standardization and environmental safety that warrant future investigation.
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Open AccessReview
On the Molecular Origin of the Toxicity of Erophaca baetica (L.) Boiss.
by
Mounia Chroho, Latifa Bouissane and Christian Bailly
Future Pharmacol. 2025, 5(2), 28; https://doi.org/10.3390/futurepharmacol5020028 - 12 Jun 2025
Abstract
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Background/Objectives: The plant species Erophaca baetica (L.) Boiss. (synonym: Astragalus lusitanicus Lam.) is found essentially around the Mediterranean basin, with Morocco as its ancestral territory. The foliage of E. baetica is toxic to small ruminants, and for this reason the plant is often
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Background/Objectives: The plant species Erophaca baetica (L.) Boiss. (synonym: Astragalus lusitanicus Lam.) is found essentially around the Mediterranean basin, with Morocco as its ancestral territory. The foliage of E. baetica is toxic to small ruminants, and for this reason the plant is often eliminated by farmers, despite its ecological and medicinal potential. The phytochemicals at the origin of the toxicity of E. baetica are not precisely known, but several potentially toxic products have been identified. In particular, aliphatic nitro compounds are present in the aerial parts of the plant, such as 3-nitro-propionic acid (NPA) and its precursor 3-nitro-propanol (NPOH) which are most likely at the origin of the plant toxicity. Results: The present review provides a detailed analysis of the nitrotoxins isolated from E. baetica and their mechanism of action. The covalent targeting of metabolic enzymes such as isocitrate lyase and succinate dehydrogenase by NPA is discussed. The mitochondrial chain blocker NPA is most likely responsible for the brain toxicity of E. baetica, but the presence of other potentially toxic chemicals—such as lusitoxamine and lusitoxamide—is also discussed. Conclusions: This review shed light on the widespread but little-known Mediterranean plant E. baetica and the phytochemicals responsible for the plant’s toxicity.
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Open AccessArticle
Recovery from AMPA Receptor Potentiation by Ampakines
by
Daniel P. Radin, Rok Cerne, Jodi L. Smith, Jeffrey M. Witkin and Arnold Lippa
Future Pharmacol. 2025, 5(2), 27; https://doi.org/10.3390/futurepharmacol5020027 - 31 May 2025
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Background: Ampakines are a family of molecules that enhance the functioning of AMPA-glutamate receptors (AMPAR). High-impact ampakines completely offset receptor desensitization and enhance agonist binding affinity, while low-impact ampakines only modestly affect receptor desensitization and do not alter agonist binding affinity. Nonetheless, little
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Background: Ampakines are a family of molecules that enhance the functioning of AMPA-glutamate receptors (AMPAR). High-impact ampakines completely offset receptor desensitization and enhance agonist binding affinity, while low-impact ampakines only modestly affect receptor desensitization and do not alter agonist binding affinity. Nonetheless, little is known about AMPAR recovery following ampakine treatment. Methods: Herein, we study the effects of ampakines on AMPAR recovery and the interaction between high- and low-impact ampakines. Results: The high-impact ampakine CX729 did not induce any current in the absence of glutamate, but it dramatically increased glutamate-induced steady-state inward currents. Recoveries from the enhancement were significantly slower than those for the low-impact ampakine CX516, as was also seen on miniature synaptic currents. Electrophysiological interaction studies suggest that high- and low-impact ampakines may have different binding sites. We further investigated the induction of the potentiated response by measuring glutamate-induced responses after transient applications of CX729 or CX729 plus glutamate. Under both circumstances, subsequent application of glutamate yielded comparably potentiated responses. Furthermore, the recovery time was not different if saline was substituted for glutamate during the recovery period. Conclusions: These observations show that AMPAR potentiation by CX729 does not require the simultaneous presence of glutamate, nor is the slow reversal of the effects of the ampakine altered by subsequent receptor activation. Hence, the slow recovery from the effects of these select ampakines on the AMPAR may be the result of slow dissociation kinetics. We posit that the slow recovery of AMPAR from high-impact ampakines may contribute to the seizurogenic effects of this drug class and that high-impact ampakines that allow for more rapid AMPAR recovery may be safer and more clinically viable candidates.
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Open AccessArticle
Safety Toxicology Study of Reassortant Mopeia–Lassa Vaccine in Guinea Pigs
by
Bradley S. Wahle, Peter Pushko, Katie Albanese, Dylan M. Johnson, Irina Tretyakova, Igor S. Lukashevich and Thomas Rudge
Future Pharmacol. 2025, 5(2), 26; https://doi.org/10.3390/futurepharmacol5020026 - 31 May 2025
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(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice.
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(1) Background: Mopeia–Lassa reassortant ML29 virus is an investigational, reassortant virus vaccine for the prevention of Lassa fever caused by Lassa virus (LASV). (2) Methods: The vaccine virus ML29-SF was prepared in Vero cells using a serum-free culture medium under Good Manufacturing Practice. A 2-week repeat dose toxicity study was performed in guinea pigs under Good Laboratory Practice (GLP) regulations to assess the local and systemic toxicological effects. (3) Results: Following an intramuscular (IM) or subcutaneous (SC) injection of 104 PFU of ML29-SF LASV vaccine at the start of the study, with a second dose 15 days later, no toxicological response attributable to the vaccine was observed. Vaccine-related effects were not observed in any in-life or post-mortem parameter evaluated, including clinical observations, injection site observations, body temperature, body weight, food consumption, ophthalmology, immunology, hematology, clinical chemistry, gross anatomical pathology, organ weights, and histopathology. An immunogenic response, as measured by the elicitation of IgG antibodies against major LASV immunogens, nucleocapsid and glycoprotein precursor, was observed in all vaccine-treated animals prior to the booster dose (Study Day 15) which endured through the end of the study (Study Day 42). There was no evidence of viral shedding in any vaccinated animal. (4) Conclusions: Overall, this single-dose vaccine was locally and systemically well tolerated even after a two-dose repeat administration, confirming the high level of safety of ML29-SF vaccination and supporting the future evaluation of this LASV vaccine, including in clinical trials.
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