Current Drug Targets[JOURNAL]
Sun
200 papers
Targeting the Toll-like Receptor Signaling Pathway in Lung Cancer: Therapeutic Opportunities and Challenges.
Usama M, Raza B, Wu M … +1 more , Ji S
Curr Drug Targets · 2025 · PMID 40916441 · Publisher ↗
Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking i...
Lung cancer, particularly non-small cell lung cancer, is a leading cause of global mortality, with many cases diagnosed at advanced stages. The Toll-Like Receptor (TLR) signaling pathway plays a crucial role in linking inflammation to lung cancer progression, with both pro-tumor and anti-tumor effects. This perspective delves into the complex functions of TLR proteins in lung cancers, elucidating their involvement in tumor growth, angiogenesis, and metastasis. In addition, we highlight the therapeutic potentials of TLR agonists and antagonists, emphasizing their interplay with immune checkpoint inhibitors like PD-1/PD-L1 blockers to overcome immunosuppressive barriers. Nevertheless, the paradoxical effects of TLR activation, balancing immune stimulation and suppression, demand precise targeting strategies. Collectively, our study synthesizes the current understanding of TLR signaling pathways in lung cancers, offering insights into their potential for advancing lung cancer therapies.
A Review of Amylin Peptide Receptor Activators for Obesity Pharmacotherapy.
Lee S
Curr Drug Targets · 2025 · PMID 40910290 · Publisher ↗
Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestin...
Amylin is a thirty-seven amino acid peptide hormone that is secreted from the pancreas with insulin. The peptide hormone amylin activates its receptors in the brain to regulate blood glucose and food appetite. Interestingly, the amylin receptor is the heterodimer of the calcitonin receptor (which is the receptor for the peptide hormone calcitonin) and an accessory protein called receptor activity-modifying protein. Amylin receptor activation has emerged as a promising drug target for the treatment of diabetes and obesity. Recent pharmaceutical efforts with amylin receptor activators have focused on developing drugs for the treatment of obesity. Multiple amylin analogs have been tested in pre-clinical settings, and some are currently being tested in clinical trials. For this review, recent research publications and available information regarding drug development targeting amylin receptors were collected. This review summarizes the amylin receptor activators currently being tested in clinical trials for the treatment of obesity. In addition, recent research achievements were demonstrated, such as the introduction of mutations that enhanced receptor affinity/potency and the development of a method for measuring selective amylin receptor activation. Potential issues along with peptide drug development were described, including lipidation to achieve a long-acting property. The combination of an amylin analog and other anti-obesity peptide drugs has demonstrated higher clinical efficacy in reducing body weight than monotherapy. The combination therapy is likely to be the first drug therapy where an amylin analog is used for obesity treatment. In addition, amylin receptor activators may have an adverse effect profile more favorable than that of GLP-1 receptor activators, which could be a potential benefit of amylin receptor activators.
Betaine, a Potential Therapeutic Alternative for the Treatment of Depression.
Zhang YY, Cheng YY, Guan W
Curr Drug Targets · 2025 · PMID 40910212 · Publisher ↗
Depression is a debilitating psychiatric disorder characterized by loss of interest, anhedonia, and social isolation, which is projected to become the leading cause of disability worldwide by 2030. Despite the greater ec...
Depression is a debilitating psychiatric disorder characterized by loss of interest, anhedonia, and social isolation, which is projected to become the leading cause of disability worldwide by 2030. Despite the greater economic and social burden imposed by depression, the precise pathophysiology underlying the development of depression remains elusive. Betaine (N, N, N-trimethylglycine), an amino acid derivative, is widely distributed in various animals and plants and has been shown to have numerous beneficial effects, including antioxidant activities, anti-inflammatory functions, regulation of energy metabolism, and reduction of endoplasmic reticulum stress. It has been used to treat Alcohol-Associated Liver Disease (AALD), type 2 diabetes, cancer, obesity, and Alzheimer's Disease (AD). Interestingly, accumulating evidence has shown that betaine exerts a significant role in alleviating depressive-like behavior in patients and animals resulting from chronic stress. Although the antidepressant effects of betaine have not been compared with traditional antidepressants with insufficient verification, based on the neurobiological mechanisms of depression, it may be a potential alternative medicine for the treatment of depression. This is the first review aiming to provide a comprehensive overview of the remarkable effects of betaine in the pathophysiology of depression. These pieces of evidence are of great importance for deepening our understanding of the antidepressant mechanism of betaine, so as to develop betaine supplements for the supplementary treatment of depression.
Sepsis-Associated Brain Dysfunction: Mechanisms, Clinical Insights, and Therapeutic Strategies.
Payal N, Saxena J, Srivastava VK … +6 more , Kaushik S, Siddiqui AJ, Chauhan K, Sharma A, Jyoti A, Sharma L
Curr Drug Targets · 2025 · PMID 40908529 · Publisher ↗
Sepsis is a lethal clinical condition representing severe inflammation and immune suppression to pathogen or infection, leading to tissue damage or organ dysfunction. Hyper-inflammation and immune suppression cause a fat...
Sepsis is a lethal clinical condition representing severe inflammation and immune suppression to pathogen or infection, leading to tissue damage or organ dysfunction. Hyper-inflammation and immune suppression cause a fatal, escalated Blood-Brain Barrier permeability, being a secondary response towards infection resulting in sepsis-associated brain dysfunction. These changes in the BBB lead to the brain's susceptibility to increased morbidity and mortality. An important mechanism of sepsis-associated brain dysfunction includes excessive activation of microglial cells, altered brain endothelial barrier function, and BBB dysfunction. Lipopolysaccharide, a bacterial cell wall component (endotoxin), by forming a complex through membrane- bound CD receptors on macrophages, monocytes, and neutrophils, begins synthesizing anti- inflammatory agents for defense of the host, including nitric oxide, cytokines, chemokines, interleukins, and the complement system. Unrestrained endotoxemia and pro-inflammatory cytokines result in microglial as well as brain endothelial cell stimulation, downregulation of tight junctions, along with intense recruitment of leucocytes. Subsequent neuroinflammation, together with BBB dysfunction, aggravates brain pathology as well as worsens sepsis-associated brain dysfunction. The clinical demonstration includes mild (confusion and delirium) along with severe (cognitive impairment, coma, as well as sequel death). Different clinical neurophysiological evaluation parameters can be used for the quantification and important issues of the disorder, including SOFA, imaging methods, and the use of biomarkers associated with brain dysfunction. The present review addresses the mechanism, clinical examination, the long-term cognitive effects, and current treatment modalities for sepsis-associated brain dysfunction.
Development of Novel Intravesical Formulation for Bladder Retention Targeting Bladder Disorders.
Harle V, Agrawal YO
Curr Drug Targets · 2025 · PMID 40776648 · Publisher ↗
Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's di...
Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's distinct anatomy successfully prevents any hazardous material from entering circulation. The pathogenesis was assessed according to the extent of invasion in the bladder wall tissue obtained through Transurethral Resection of Bladder Tumor (TURBT) and classified as Muscle-Invasive and Non-Muscle Invasive Bladder Cancer (MBIC and NMIBC). Intravesical Drug Delivery (IDD) has recently gained attention for treating bladder disorders. IDD refers to the insertion of a drug directly into the bladder using a catheter. Intravesical administration of immunotherapy or chemotherapy has been demonstrated to reduce recurrence rates and inhibit disease progression. In addition, several other systems, including recombinant BCG, gene therapy, vectors, and Antibody-Drug Conjugates (ADCs), are now used. Moreover, the novel intravesical formulations of distinct chemotherapeutic agents, including gemcitabine, Doxorubicin (DOX), and Mitomycin C (MMC), are used in bladder-related problems. Novel intravesical drugs, polymeric hydrogels, dendrimers, hydrogels, mucoadhesives, nanocarriers, and intravesical devices have been discussed. Aside from chemotherapy and immunotherapy, devices such as Gem- RIS, device-assisted hyperthermic intravesical chemotherapy, and photodynamic therapy are utilized.
Gut-Brain Dialogues in Fruit Fly (): How Peptide Hormones Bridge Metabolism, Longevity, and Behavioral Adaptation.
Tian M, Sun S, Meng Q … +6 more , Li J, Li X, Ren S, Huang Z, Du S, Wang Y
Curr Drug Targets · 2025 · PMID 40776647 · Publisher ↗
BACKGROUND: Gut-peptide hormones are crucial regulators of various physiological processes, including metabolism, digestion, behavior, and homeostasis. In Drosophila melanogaster, a widely used model organism, a diverse...
BACKGROUND: Gut-peptide hormones are crucial regulators of various physiological processes, including metabolism, digestion, behavior, and homeostasis. In Drosophila melanogaster, a widely used model organism, a diverse range of gut-peptide hormones governs gut-brain communication, influencing food intake, energy balance, circadian rhythms, stress responses, and aging. OBJECTIVE: This review summarizes recent studies on gut-peptide hormones in D. melanogaster, focusing on their mechanisms of action, interactions with other signaling pathways, and their relevance to human orthologs. METHODS: The PubMed database was searched for studies on gut-peptide hormones in D. melanogaster published in the past decade. RESULTS: The functions of D. melanogaster gut-peptide hormones were reviewed, including DH31, Bursicon (Burs), Tachykinins (Tks), Hedgehog (Hh), Pigment-dispersing factor (PDF), Neuropeptide F (NPF), Short neuropeptide F (sNPF), Allatostatins (ASTs), CCHamides (CCHa), and Limostatin (Lst). These hormones regulate key physiological processes such as digestion, energy homeostasis, and metabolism through conserved pathways. CONCLUSION: Drosophila melanogaster gut-peptide hormones are fundamental regulators of health and disease. They are conducive to exploring conserved mechanisms for developing treatments against human metabolic and aging disorders.
Role of Artificial Intelligence in Nanomedicine and Organ-specific Therapy: An Updated Review.
Rajpoot K
Curr Drug Targets · 2025 · PMID 40698694 · Publisher ↗
BACKGROUND: In organ-specific therapy, artificial intelligence (AI) is primarily used to improve surgical planning through image analysis, predict post-transplant outcomes, personalize treatment plans based on patient da...
BACKGROUND: In organ-specific therapy, artificial intelligence (AI) is primarily used to improve surgical planning through image analysis, predict post-transplant outcomes, personalize treatment plans based on patient data, optimize organ allocation logistics, and donor-recipient precision mapping for organs to improve transplants. Furthermore, all these applications ultimately lead to better patient outcomes and enhanced organ therapy. OBJECTIVE: This review aims to examine the revolutionary effects of AI in some key healthcare fields, such as nanomedicine, cancer treatment, clinical applications, and organ-specific delivery. METHODS: This review article discusses in detail the role of AI in nanomedicine, cancer therapy, clinical applications, organ-specific delivery (e.g., cardiovascular, gastroenterology, kidney, liver, lung, ophthalmology, skin, etc.), diagnosis, and radiotherapy. In addition, it also discusses limitations and challenges of AI in healthcare. RESULTS: AI-based clinical translation has potential but faces challenges like artifact vulnerability, ethical and legal considerations, and security measures. Restrictive data-use policies may hinder accurate analysis. Regulations and collaboration with data-sharing mechanisms could overcome barriers. CONCLUSION: AI is being utilized in organ-specific therapy to enhance donor-recipient matching, surgical planning, post-transplant outcomes prediction, and personalized treatment plans by analyzing patient data.
Modern Solutions to UTIs: The Role of Nanotechnology and Herbal Treatments.
Kumar A, Kumar A, Islam MM … +2 more , Borgohain R, Raikwar S
Curr Drug Targets · 2025 · PMID 40696550 · Publisher ↗
INTRODUCTION: Urinary tract infections (UTIs) range from mild to severe cases, commonly caused by uropathogenic Escherichia coli (E. coli). The growing concern about antibiotic resistance demands alternative treatment st...
INTRODUCTION: Urinary tract infections (UTIs) range from mild to severe cases, commonly caused by uropathogenic Escherichia coli (E. coli). The growing concern about antibiotic resistance demands alternative treatment strategies. Nanotechnology, particularly nanocarriers, presents a promising solution by enhancing drug delivery, antibacterial activity, and targeted therapy. This review focuses on the emerging role of combining herbal remedies with nanotechnology for more effective and personalized management of UTIs, aiming to overcome the limitations of conventional antibiotic therapies. METHODS: The review involved an extensive search of scientific databases and relevant literature, including studies published to date from PubMed, Science Direct, and Google Scholar. Urinary tract infections (UTI), antibiotic resistance, nanotechnology, drug delivery, targeted drug delivery, and herbal drugs were among the search phrases used. RESULTS: According to studies, combining herbal extracts such as neem and turmeric with nanotechnology significantly enhances antimicrobial activity against UTI pathogens. These nanoformulations show enhanced bacterial inhibition, reduced inflammation, and increased therapeutic precision with minimal side effects. DISCUSSION: The synergistic use of herbal remedies and nanocarriers offers a novel approach to managing UTIs. Nanotechnology not only enhances drug delivery but also improves diagnostic accuracy through fluorescence markers and biomolecule tagging. This strategy effectively addresses growing antibiotic resistance and supports the development of personalized treatments. The combination of natural bioactives and advanced delivery systems offers a safer, more effective alternative to conventional antibiotics in treating UTIs. CONCLUSION: The integration of nanotechnology and herbal therapies revolutionizes UTI management through precision medicine. This approach enhances treatment efficacy, diagnostic accuracy, and patient outcomes, offering a personalized solution to combat antibiotic resistance and urinary tract abnormalities with improved targeting and minimal side effects.
Innovative Strategies and Advances in Drug Delivery Systems to Address Poor Solubility: A Comprehensive Review.
Bakrey H, Abdu A, Shivgotra R … +4 more , Soni B, Sharma M, Bakrey A, Jain SK
Curr Drug Targets · 2025 · PMID 40696549 · Publisher ↗
Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with...
Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with bioavailability, such as poor, inconsistent, limited, and highly variable bioavailability of marketed products. It is estimated that 40% of marketed drugs face bioavailability challenges primarily due to poor water solubility, and about 90% of pharmacological compounds exhibit poor water solubility in their early development stages. Addressing this issue is crucial for improving drug performance, efficacy, and patient outcomes. This review provides an overview of the challenges associated with poorly soluble drugs, including low bioavailability, limited dissolution rates, inconsistent absorption, decreased patient compliance, formulation difficulties, and associated costs and time constraints. Numerous strategies have been now investigated to tackle the issue of poor solubility. This review offers an updated overview of commonly used macro and nano drug delivery systems, including micelles, nanoemulsions, dendrimers, liposomes, lipid-based delivery systems, microemulsions, cosolvents, polymeric micelle preparation, drug nanocrystals, solid dispersion methods, crystal engineering techniques, and microneedle- based systems. Additionally, the review examines advanced techniques like cyclodextrin- based delivery systems, co-solvency and co-crystallization approaches, polymeric micelles, spray drying, co-precipitation, and amorphous solid dispersion. The role of computational modeling and formulation prediction is also addressed. Recent advancements in protein-based approaches, 3D printing, mesoporous silica nanoparticles, supramolecular delivery systems, magnetic nanoparticles, nanostructured lipid carriers, and lipid-based nanoparticles are highlighted as novel solutions for enhancing the solubility of poorly soluble drugs. The review concludes with predictions for the future, emphasizing the potential for further innovation in drug delivery methods to overcome the challenges associated with poorly soluble drugs.
Therapeutic Drug Monitoring: A New Hope for Individualised Treatment with Venetoclax.
Tang Y, Li S, Rao P … +3 more , Yu W, Jiang X, Liu J
Curr Drug Targets · 2025 · PMID 40676794 · Publisher ↗
B-cell lymphoma-2 (BCL-2) plays a key role in regulating apoptosis. Venetoclax (VEN), a BCL-2 inhibitor, has been approved for the treatment of a variety of hematologic malignancies. VEN is primarily metabolized by CYP3A...
B-cell lymphoma-2 (BCL-2) plays a key role in regulating apoptosis. Venetoclax (VEN), a BCL-2 inhibitor, has been approved for the treatment of a variety of hematologic malignancies. VEN is primarily metabolized by CYP3A, and a variety of factors (such as CYP3A inhibitors, as well as food and hepatic functions) have been reported to significantly influence the metabolic process. There is significant interindividual variability in VEN plasma concentrations, and studies have shown that its exposure levels are correlated with efficacy, although the relationship with adverse effects remains controversial. The value of applying of therapeutic drug monitoring (TDM) in individualized VEN therapy has been confirmed by some studies, but the optimal therapeutic window for different malignancies is still unclear. This review summarizes the pharmacokinetic characteristics, along with the factors influencing VEN pharmacokinetics, drug-drug interactions, and advancements in TDM research on VEN, aiming to provide a theoretical basis for TDM-guided individualized therapy.
Crossing Boundaries: A Review of the Diverse Functions of Heterocyclic Compounds in the Management of Cancer and Infectious Diseases.
Wal P, Wal A, Jawaid T … +6 more , Ganguly P, Patel B, Nainwal P, Lari MQ, Kumar A, Kumar D
Curr Drug Targets · 2025 · PMID 40641030 · Publisher ↗
INTRODUCTION/OBJECTIVE: Heterocyclic molecules, a mainstay of contemporary medicinal chemistry, are essential in developing antibacterial and anticancer treatments. Their distinct structural features-one or more heteroat...
INTRODUCTION/OBJECTIVE: Heterocyclic molecules, a mainstay of contemporary medicinal chemistry, are essential in developing antibacterial and anticancer treatments. Their distinct structural features-one or more heteroatoms within the ring-allow for a wide range of biological activities. With a focus on their modes of action and insights into the structure-activity relationship (SAR), this study examines the therapeutic uses of heterocyclic compounds in antibacterial, antifungal, antiviral, and anticancer treatments. METHODS: The review uses search engines like PubMed and Google Scholar, with a preference for English as the major language, to gather and analyse recent research on the antibacterial and anticancer applications of diverse heterocyclic compounds. RESULTS: It has been discovered that heterocyclic chemicals are useful in blocking microbial enzymes, including DNA gyrase and the machinery involved in protein synthesis. Heterocyclic compounds such as benzimidazoles, quinolines, and acridines have demonstrated noteworthy efficacy in cancer therapy through their targeting of tubulin inhibition, DNA intercalation, and signalling pathways like PI3K/Akt/mTOR and MAPK. The pharmacological characteristics of these compounds were improved by the addition of electron-withdrawing groups, halogenation, and heteroatom replacements, according to SAR investigations. CONCLUSION: Heterocyclic compounds have great promise for antibacterial and anticancer treatments. They are crucial in drug development because of their structural flexibility, which enables the targeted suppression of vital biological processes. The effectiveness of heterocyclic compounds will continue to be improved by ongoing advancements in drug design and SAR optimization, opening new possibilities for the creation of more potent and selective medicinal treatments.
Matrix Metalloproteinase-9: A Key Diagnostic Biomarker in Cancer Progression.
Srivastava A, Gupta J, Singhal S … +7 more , Tulli H, Mishra N, Atale N, Jain BP, Grosset C, Saxena B, Rani V
Curr Drug Targets · 2025 · PMID 40621756 · Publisher ↗
Matrix metalloproteinase-9, also known as MMP-9, gelatinase B, or 92 kDa type IV collagenase, is an enzyme that belongs to the matrix metalloproteinase (MMP) family. It is involved in the remodeling of the extracellular...
Matrix metalloproteinase-9, also known as MMP-9, gelatinase B, or 92 kDa type IV collagenase, is an enzyme that belongs to the matrix metalloproteinase (MMP) family. It is involved in the remodeling of the extracellular matrix in various physiological and pathological processes. MMPs are expressed in low, tightly regulated concentrations; their overexpression or dysregulation can lead to diseases, including cancer. MMP-9 is increasingly recognized as a significant drug target in cancer therapy due to its involvement in tumorigenesis, including processes like cell migration, angiogenesis, and pro-apoptotic and anti-apoptotic activities. Despite MMP-9's significance as a cancer target, developing effective inhibitors remains challenging due to MMP structural similarities. Utilizing MMP-9 as a cancer biomarker could advance cancer diagnosis, prognosis, disease monitoring, recurrence prediction, and other procedures. Biosensors are emerging as pivotal tools in cancer diagnosis and treatment, leveraging their ability to detect specific biomarkers associated with various cancers. Recent advancements have led to the development of both cleavage-based and non-cleavage-based biosensors that enable rapid and sensitive analysis at clinically relevant concentrations of biomarkers while allowing specificity and low detection limits, enhancing point-of-care diagnostics. The cleavage-based biosensors leverage the enzymatic activity of MMP-9, utilizing substrates that are specifically cleaved by MMP-9, while the non-cleavage- based biosensors employ affinity methods, such as antibodies and aptamers for detection. The present review aims to evaluate the role of MMP-9 as a significant biomarker in cancer and its detection through innovative biosensor technologies, while exploring its involvement in various cancer- related processes. This review discusses the significance of MMP-9 in cancer progression, highlighting clinical trials that assess MMP-9 inhibitors as potential therapeutic agents to halt metastatic spread. Furthermore, MMP-9 is detected via biosensors, and insights into the translational potential of MMP-9 both as a biomarker for early cancer detection and a viable target for therapeutic intervention are provided, ultimately contributing to improved patient outcomes in oncology.
GSTP1, PRDX2 and NFE2L2: Potential Markers for Primary Stage Breast Cancer.
Jaffari SAZ, Haider F, Syed N … +6 more , Ilyas A, Idrees F, von Kriegsheim A, Krishnankutty R, Nawab SN, Hashim Z
Curr Drug Targets · 2025 · PMID 40621755 · Publisher ↗
INTRODUCTION: Breast cancer incidence and mortality have continued to rise over the past few decades. Despite advancements made in clinical research, the most imperative feature of breast cancer management is the diagnos...
INTRODUCTION: Breast cancer incidence and mortality have continued to rise over the past few decades. Despite advancements made in clinical research, the most imperative feature of breast cancer management is the diagnosis at the earliest stages. The current focus of the study is to identify and quantify differentially expressed oxidative stress-related proteins as putative early- stage markers for breast cancer. METHODS: Normal and cancerous breast tissue samples (n = 40) were collected after approval from the institutional bioethics committee (IBC) and with patient's consent. A label-free proteomic approach was used to quantify oxidative stress-related proteins. Gene expression of GSTP1, PRDX2, HSP90, NFE2L2, and miR-365a was quantified using RT-qPCR in all samples. Protein expression of PRDX2 and GSTP1 was further analyzed using immunohistochemistry. RESULTS: The protein and gene expression of PRDX2, GSTP1, and HSP90 were significantly upregulated (p < 0.05) in cancerous samples as compared to normal. However, gene and protein expression of the transcription factor NFE2L2 was significantly downregulated (p < 0.05) in diseased samples. OncomiR-365a was also significantly upregulated (p < 0.05) in cancerous samples. Immunohistochemical analysis also confirmed the upregulated expression of GSTP1 and PRDX2 in cancer tissues. DISCUSSION: Our study provides insight into the significant role of GSTP1, PRDX2, and NFE2L2 in the pathophysiology of the disease as early-stage breast cancer markers. It is suggested that altered expression of these key proteins could play a protective role in reducing the damage. CONCLUSION: It can be concluded that GSTP1, PRDX2, and NFE2L2 may serve as predictive early- stage markers for diagnosis and potential therapeutic targets for breast cancer.
RMNet: An RNA m6A Cross-species Methylation Detection Method for Nanopore Sequencing.
Li Q, Sun C, Wang D … +1 more , Lou J
Curr Drug Targets · 2025 · PMID 40621754 · Publisher ↗
INTRODUCTION: N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic cells, influencing RNA lifecycle processes. Existing m6A detection methods, such as wet-lab techniques and statistical approache...
INTRODUCTION: N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotic cells, influencing RNA lifecycle processes. Existing m6A detection methods, such as wet-lab techniques and statistical approaches, are time-consuming, labor-intensive, or require control samples, while machine learning models often lack cross-species applicability. This study aims to develop RMNet, a robust cross-species m6A detection method using nanopore sequencing. METHODS: RMNet employs Conformer and RNN architectures, integrating signal and alignment features from nanopore sequencing data. Contrastive learning enhances differentiation between m6A and non-m6A sites. The model was trained and tested on datasets from synthesized RNA, Arabidopsis, and human samples, using a single set of model weights. RESULTS: RMNet achieved state-of-the-art performance with accuracies of 99.7% for synthesized RNA, 78.8% for Arabidopsis, and 88.9% for human datasets. It outperformed existing methods (m6Anet, DENA, and RedNano) across six metrics, including AUC and AUPR, demonstrating robust cross-species generalization. DISCUSSION: RMNet's ability to detect m6A sites across diverse species with a single model addresses limitations of species-specific models. Its high sensitivity and feature representation enable applications in cancer research, neurodevelopmental studies, and plant biology. Limitations include higher error rates in human datasets for thymine-rich k-mers, likely due to complex secondary structures. CONCLUSION: RMNet provides an efficient, powerful tool for cross-species m6A detection, advancing epitranscriptomics research with potential applications in precision medicine and agricultural science.
Lipidomics in Breast Cancer: Decoding Metabolic Reprogramming and Unlocking Therapeutic Opportunities.
Singhai H, Rathee S, Patil UK
Curr Drug Targets · 2025 · PMID 40600551 · Publisher ↗
Lipidomics, a cutting-edge branch of metabolomics provides a comprehensive understanding of the lipidome and its alterations in cellular and systemic processes. In Breast Cancer (BC), a highly heterogeneous disease, lipi...
Lipidomics, a cutting-edge branch of metabolomics provides a comprehensive understanding of the lipidome and its alterations in cellular and systemic processes. In Breast Cancer (BC), a highly heterogeneous disease, lipidomics has emerged as a pivotal tool for exploring metabolic reprogramming, tumor progression, and therapeutic resistance. This review highlights the intricate relationship between lipid metabolism and breast cancer, with a focus on subtype-specific lipid dependencies, oxidative stress, and ferroptosis. Technological advancements, such as mass spectrometry and chromatography, have enabled precise profiling of lipid alterations, revealing distinct lipid signatures across breast cancer subtypes. Key enzymes like acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), along with lipid regulators like PPARγ, have been identified as central players in lipid-driven tumorigenesis. Lipidomic studies offer the potential for biomarker discovery and the development of lipid-targeted therapies. Despite challenges in standardization and integration with other omics approaches, lipidomics is poised to revolutionize breast cancer diagnostics and therapeutics, providing novel insights into the metabolic underpinnings of this complex disease.
Advancing Amyloid Aggregation Research: A Focus on Innovative Therapies, Molecular Modeling and Nano-Delivery Systems in Alzheimer's Disease.
Hasan U, Jain H, Ali R
Curr Drug Targets · 2025 · PMID 40600550 · Publisher ↗
INTRODUCTION: Alzheimer's disease (AD), the most common form of dementia, is a major global health issue. Its complex pathology, including amyloid-beta (Aβ) aggregation, leads to neuronal damage and cognitive decline. Si...
INTRODUCTION: Alzheimer's disease (AD), the most common form of dementia, is a major global health issue. Its complex pathology, including amyloid-beta (Aβ) aggregation, leads to neuronal damage and cognitive decline. Since Aβ plays a major role in AD, therapies targeting its production, aggregation, and clearance are being actively explored. This review discusses recent advances in gene therapy, enzyme inhibitors, molecular modeling, and nano-delivery systems aimed at modifying AD progression, highlighting their potential and challenges. METHODS: This review compiles findings on BACE1 and γ-secretase inhibitors, gene therapies that modify amyloid metabolism, and combination therapies. Studies have been selected based on their focus on Aβ regulation and their impact on disease progression, cognitive function, and breakthroughs in diagnostics, molecular modeling, and drug delivery for neurodegenerative conditions. RESULTS: BACE1 inhibitors, such as verubecestat, and γ-secretase inhibitors, shows potential, however, they face significant challenges related to BBB penetration and adverse effects. Gene therapies using AAV vectors and CRISPR/Cas9 technologies are promising, particularly for individuals genetically predisposed to these diseases. Combination therapies targeting amyloid, tau, and neuro-inflammation have emerged as effective approaches. Advancements in PET, SPECT, MRI, small molecule probes, molecular modeling, and nano-particle-based drug delivery are improving diagnostic and treatment options. DISCUSSION: The findings emphasize the multifactorial complexity of amyloid disorders and the limitations of mono-therapies. While certain agents demonstrated efficacy in early disease stages, most treatments have failed in advanced phases due to poor central nervous system (CNS) bioavailability, adverse effects, or insufficient target engagement. Novel delivery systems, combination therapies, and computational design approaches offer enhanced translational potential. However, challenges such as immune responses, delivery efficiency, and off-target effects continue to pose significant barriers. CONCLUSION: Aβ-targeted therapies, including enzyme inhibitors and gene therapies, hold promise, though challenges such as BBB penetration and toxicity still remain. Combination therapies, along with advancements in diagnostics and drug delivery technology, are essential for finding effective treatments for Alzheimer's, Parkinson's, and other neurodegenerative diseases. Future research should prioritize overcoming the persistent barriers to BBB penetration, enhancing therapeutic selectivity, and refining drug delivery systems to enable more precise, targeted interventions, to ultimately reduce the progression of disease at the molecular level.
The Role of PGE2 in Age-related Diseases.
Guan J, Chen C, Wu S … +1 more , Zhu H
Curr Drug Targets · 2025 · PMID 40600549 · Publisher ↗
In the past several years, human life expectancy has increased dramatically, and the global aging process is accelerating at an unprecedented rate. Impaired organ functions and systemic inflammation increase the risk of...
In the past several years, human life expectancy has increased dramatically, and the global aging process is accelerating at an unprecedented rate. Impaired organ functions and systemic inflammation increase the risk of aging-related diseases. It seriously affects the quality of life in older adults and places a heavy burden on the global economy and public health. Inflammation is the cornerstone of many age-related diseases, and among various inflammatory mediators, Prostaglandin E2 (PGE2) has emerged as a key player. For example, PGE2 could participate in the progression of Alzheimer's disease (AD) by modulating neuroinflammation. Plasma PGE2 is regarded as a potential and specific diagnostic biomarker, and higher initial PGE2 levels are positively correlated with longer survival in AD. PGE2 also mediates bone and muscle metabolism to affect age-related musculoskeletal diseases, including sarcopenia, osteoporosis, and osteoarthritis. It activates the EP4 receptor on sensory nerves to inhibit sympathetic nerve activity and modulate bone formation. Moreover, the PGE2/EP4 axis positively regulates muscle mass and strength. In diabetes, increased Cox-2 and m-PGES2 promote PGE2 production. The activated PGE2/EP3 axis exacerbates the progression of type 2 diabetes (T2D) by impairing glucose metabolism and accelerating β-cell senescence. Therefore, the role of PGE2 in age-related diseases deserves greater attention. Its involvement is driven by the dysregulation of its biosynthesis, metabolism, and receptor- mediated signaling. Regulating the concentration of PGE2 or modulating receptor activity represents a promising therapeutic strategy for managing age-related diseases.
Targeting Creatine and Creatine Kinase in Cancer: Exploring Potential Therapeutic Strategies.
Abdollahzadeh M, Ghodsi R, Taherzadeh Z … +1 more , Hatamipour M
Curr Drug Targets · 2025 · PMID 40600548 · Publisher ↗
Creatine kinases (CKs) are a family of vital enzymes implicated in the domain of cellular bioenergy, fulfilling a pivotal role in facilitating the reversible transfer of phosphoryl groups between adenosine triphosphate (...
Creatine kinases (CKs) are a family of vital enzymes implicated in the domain of cellular bioenergy, fulfilling a pivotal role in facilitating the reversible transfer of phosphoryl groups between adenosine triphosphate (ATP) and creatine. This process plays a crucial role in maintaining optimal ATP levels during energy-demanding processes, a requirement that is amplified in rapidly proliferating cells, including cancerous cells. CKs are pivotal in supporting cancer growth and metastasis, making their inhibition a promising therapeutic strategy. The present review discusses a few ways of disrupting the creatine energy production cycle with emphasis on three main areas of research: First, we consider the different strategies that attack the Creatine Transporter (SLC6A8). Since this transporter facilitates the entry of creatine into the cell, it is expected that inhibiting this transporter may lead to reduced availability of creatine for CK-mediated energy production. Second, strategies aimed at directly inhibiting the enzyme carrying out the creatine phosphorylation are described. Lastly, we consider approaches targeting the backward reaction, i.e., the re-conversion of phosphocreatine to creatine and, thereby, the equilibrium of the CK reaction. The current review gives an overview of the structure-activity and structure-property relationships of the currently available CK inhibitors. Understanding these relations in depth is a prerequisite for developing new and more potent and selective CK inhibitors. This review focuses on an in-depth analysis to create better CK inhibitors with possible applications in oncology.
RAAS Overactivation and Mitochondrial Damage Signaling as Key Players in Lethal COVID-19.
Fulkerson S, Hohman G, Stark T … +2 more , Aydogdu S, Eldeeb M
Curr Drug Targets · 2025 · PMID 40444629 · Publisher ↗
Coronavirus disease 2019 (COVID-19), which led to a global pandemic causing millions of deaths, is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- -2). While previous research on COVID-19 has pri...
Coronavirus disease 2019 (COVID-19), which led to a global pandemic causing millions of deaths, is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- -2). While previous research on COVID-19 has primarily utilized nasal swabs and blood samples, these do not provide comprehensive insights into all the organ systems affected by the infection. A recent study by Topper et al. addressed this gap by analyzing both nasal samples and autopsy tissues from SARS-CoV-2-infected individuals. Their findings highlight a significant role of mitochondrial damage pathways and RAAS overactivation in contributing to the severity of SARSCoV- 2 infections. Importantly, targeting mitochondrial dysfunction and RAAS overactivation pathways may offer promising and specific druggable targets for treating COVID-19 patients.
Neurostimulation for the Management of Epilepsy: Advances in Targeted Therapy.
Verma S, Malviya R, Sridhar SB … +2 more , Sundram S, Shareef J
Curr Drug Targets · 2025 · PMID 40444628 · Publisher ↗
BACKGROUND: Epilepsy is a multifaceted neurological disorder marked by seizures that can present with a wide range of symptoms. Despite the prevalent use of anti-epileptic drugs, drug resistance and adverse effects prese...
BACKGROUND: Epilepsy is a multifaceted neurological disorder marked by seizures that can present with a wide range of symptoms. Despite the prevalent use of anti-epileptic drugs, drug resistance and adverse effects present considerable obstacles. Despite advancements in anti-epileptic drugs (AEDs), approximately 20-30% of patients remain drug-resistant, highlighting the need for innovative therapeutic strategies. AIM: This study aimed to explore advancements in epilepsy diagnosis and treatment utilizing modern technology and medicines. METHODS: The literature survey was carried out using Scopus, ScienceDirect, and Google Scholar. Data from the last 10 years were preferred to include in the study. RESULT: Emerging technologies, such as artificial intelligence, gene therapy, and wearable gadgets, have transformed epilepsy care. EEG and MRI play essential roles in diagnosis, while AI aids in evaluating big datasets for more accurate seizure identification. Machine learning and artificial intelligence are increasingly integrated into diagnostic processes to enhance seizure detection and classification. Wearable technology improves patient self-monitoring and helps clinical research. Furthermore, gene treatments offer promise by treating the fundamental causes of seizure activity, while stem cell therapies give neuroprotective and regenerative advantages. Dietary interventions, including ketogenic diets, are being examined for their ability to modify neurochemical pathways implicated in epilepsy. CONCLUSION: Recent technological and therapeutic developments provide major benefits in epilepsy assessment and treatment, with AI and wearable devices enhancing seizure detection and patient monitoring. Nonetheless, additional study is essential to ensure greater clinical application and efficacy. Future perspectives include the potential of optogenetics and advanced signal processing techniques to revolutionize treatment paradigms, emphasizing the importance of personalized medicine in epilepsy care. Overall, a comprehensive understanding of the multifaceted nature of epilepsy is essential for developing effective interventions and improving patient outcomes.
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