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Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.
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http://dx.doi.org/10.1016/j.drudis.2024.103979 | DOI Listing |
Eur J Med Res
September 2025
Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt.
Nuclear receptors (NRs) are a superfamily of ligand-activated transcription factors that regulate gene expression in response to metabolic, hormonal, and environmental signals. These receptors play a critical role in metabolic homeostasis, inflammation, immune function, and disease pathogenesis, positioning them as key therapeutic targets. This review explores the mechanistic roles of NRs such as PPARs, FXR, LXR, and thyroid hormone receptors (THRs) in regulating lipid and glucose metabolism, energy expenditure, cardiovascular health, and neurodegeneration.
View Article and Find Full Text PDFNat Aging
September 2025
Aging Biomarker Consortium (ABC), Beijing, China.
The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and molecular state, across diverse Chinese cohorts.
View Article and Find Full Text PDFMol Psychiatry
September 2025
Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.
Dysregulated dopaminergic signaling has been implicated in the pathophysiology of major depressive disorder (MDD) and childhood sexual abuse (CSA), but inconsistencies abound. In a multimodal PET-functional MRI study, harnessing the highly selective tracer [C]altropane, we investigated dopamine transporter availability (DAT) and resting-state functional connectivity (rsFC) within reward-related regions among 112 unmedicated individuals (MDD: n = 37, MDD/CSA: n = 18; CSA no MDD: n = 14; controls: n = 43). Striatal DAT and seed-based rsFC were assessed in the dorsal and ventral striatum and the ventral tegmental area.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, 100071, Beijing, China.
Traditional live attenuated vaccines (LAVs) are typically developed through serial passaging or genetic engineering to introduce specific mutations or deletions. While viral RNA secondary or tertiary structures have been well-documented for their multiple functions, including binding with specific host proteins, their potential for LAV design remains largely unexplored. Herein, using Zika virus (ZIKV) as a model, we demonstrate that targeted disruption of the primary sequence or tertiary structure of a specific viral RNA element responsible for Musashi-1 (MSI1) binding leads to a tissue-specific attenuation phenotype in multiple animal models.
View Article and Find Full Text PDFNat Rev Clin Oncol
September 2025
German Cancer Consortium (DKTK), Partner Site Essen, Essen, Germany.
Targeted radionuclide therapy (TRT) is a cutting-edge treatment approach in oncology that combines the molecular precision of targeted agents with the effect of radiotherapy to selectively deliver cytotoxic radiation to cancer cells. Research efforts from the past few decades have led to a diverse molecular landscape of TRT and have provided lessons for further rational development of targeted radiopharmaceuticals and expansion of the clinical applications of this treatment modality. In this Review, we discuss TRT in the context of therapeutic approaches currently available in oncology, describe the broad range of established and emerging targets for TRT including innovative approaches to exploit vulnerabilities presented by the tumour microenvironment, and address the challenges for clinical translation and molecular optimization.
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