Current Drug Targets - Online First
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21 - 29 of 29 results
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Therapeutic Drug Monitoring: A New Hope for Individualised Treatment with Venetoclax
Authors: Yue Tang, Shuojiao Li, Peng Rao, Wenxian Yu, Xuanpeng Jiang and Jiatao LiuAvailable online: 16 July 2025More LessB-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.
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Crossing Boundaries: A Review of the Diverse Functions of Heterocyclic Compounds in the Management of Cancer and Infectious Diseases
Authors: Pranay Wal, Ankita Wal, Talha Jawaid, Paramita Ganguly, Binit Patel, Pankaj Nainwal, Mohd Qasid Lari, Ajay Kumar and Dileep KumarAvailable online: 09 July 2025More LessIntroduction/ObjectiveHeterocyclic 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.
MethodsThe 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.
ResultsIt 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.
ConclusionHeterocyclic 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.
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Matrix Metalloproteinase-9: A Key Diagnostic Biomarker in Cancer Progression
Available online: 04 July 2025More LessMatrix 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.
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RMNet: An RNA m6A Cross-species Methylation Detection Method for Nanopore Sequencing
Authors: Qingwen Li, Chen Sun, Daqian Wang and Jizhong LouAvailable online: 04 July 2025More LessIntroductionN6-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.
MethodsRMNet 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.
ResultsRMNet 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.
DiscussionRMNet’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.
ConclusionRMNet provides an efficient, powerful tool for cross-species m6A detection, advancing epitranscriptomics research with potential applications in precision medicine and agricultural science.
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The Role of PGE2 in Age-related Diseases
Authors: Jun Guan, Chao Chen, Shanshan Wu and Haihong ZhuAvailable online: 24 June 2025More LessIn 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.
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Lipidomics in Breast Cancer: Decoding Metabolic Reprogramming and Unlocking Therapeutic Opportunities
Authors: Harshita Singhai, Sunny Rathee and Umesh K. PatilAvailable online: 24 June 2025More LessLipidomics, 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.
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Advancing myloid ggregation esearch: ocus n nnovative Therapies, Molecular Modeling and Nano-Delivery Systems in Alzheimer’s Disease
Authors: Umaira Hasan, Himangini Jain and Ruhi AliAvailable online: 24 June 2025More LessIntroductionAlzheimer’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.
MethodsThis 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.
ResultsBACE1 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.
DiscussionThe 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.
ConclusionAβ-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.
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IL-17 Antagonists as a Promising Therapeutic Modality for Hidradenitis Suppurativa
Authors: Piotr K. Krajewski and Jacek C. SzepietowskiAvailable online: 30 April 2025More LessHidradenitis suppurativa (HS) is an inflammatory, debilitating skin disorder affecting primarily young adults [1]. The course of the disease is chronic, with recurrent flares of inflammatory nodules, abscesses, and inflammatory tunnels localized mainly in the intertriginous areas [1]. It has been studied that HS, characterized by a high severity of pain and constant purulent discharge, has an enormous impact on a patient’s quality of life and is often associated with depression, anxiety, stigmatization, workplace challenges, and suicidal ideations [2, 3]. Due to the unknown pathogenesis and HS’s multifactorial nature, the treatment is difficult and often unsatisfactory for clinicians and patients [1, 4].
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Emerging Carbon Dots Nanomaterials for Ovarian Cancer Diagnosis and Therapy
Available online: 04 February 2025More LessDelayed diagnosis and limited treatment options make ovarian cancer difficult to treat. This paper examines the growing role of Carbon Dots (CDs) in ovarian cancer diagnosis and treatment. Photoluminescence and biocompatibility make CDs ideal for biomedical use. We emphasize their ability to improve fluorescence and molecular imaging in imaging and diagnostics. We also demonstrate the efficacy of carbon dots in targeted drug delivery systems in overcoming drug resistance and improving therapeutic outcomes. Photodynamic and photothermal therapies are used to show that CDs can treat hypoxic ovarian cancer tumours. We also discuss CD safety issues and constraints, emphasising the need for thorough assessments and fine-tuning. Future research focuses on personalised medicine and CD integration with other therapies. This text concludes by discussing CDs' clinical use and the challenges of production and regulatory approval. CDs can improve ovarian cancer diagnosis and treatment, improving patient outcomes and survival.
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