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Extensive efforts have been directed at the discovery, investigation and clinical monitoring of targeted therapeutics. These efforts may be facilitated by the convenient access of the genetic, proteomic, interactive and other aspects of the therapeutic targets. Here, we describe an update of the Therapeutic target database (TTD) previously featured in NAR. This update includes: (i) 2000 drug resistance mutations in 83 targets and 104 target/drug regulatory genes, which are resistant to 228 drugs targeting 63 diseases (49 targets of 61 drugs with patient prevalence data); (ii) differential expression profiles of 758 targets in the disease-relevant drug-targeted tissue of 12 615 patients of 70 diseases; (iii) expression profiles of 629 targets in the non-targeted tissues of 2565 healthy individuals; (iv) 1008 target combinations of 1764 drugs and the 1604 target combination of 664 multi-target drugs; (v) additional 48 successful, 398 clinical trial and 21 research targets, 473 approved, 812 clinical trial and 1120 experimental drugs, and (vi) ICD-10-CM and ICD-9-CM codes for additional 482 targets and 262 drugs against 98 disease conditions. This update makes TTD more useful for facilitating the patient focused research, discovery and clinical investigations of the targeted therapeutics. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp.
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http://dx.doi.org/10.1093/nar/gkx1076 | DOI Listing |
Acta Neuropathol Commun
September 2025
Department of Biomedical and Clinical Sciences and Department of Clinical Pathology, Linköping University, 58185, Linköping, Sweden.
Disruptions in synaptic transmission and plasticity are early hallmarks of Alzheimer's disease (AD). Endosomal trafficking, mediated by the retromer complex, is essential for intracellular protein sorting, including the regulation of amyloid precursor protein (APP) processing. The VPS35 subunit, a key cargo-recognition component of the retromer, has been implicated in neurodegenerative diseases, with mutations such as L625P linked to early-onset AD.
View Article and Find Full Text PDFJ Biomed Sci
September 2025
Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Background: PPM1D (protein phosphatase Mg⁺/Mn⁺ dependent 1D) is a Ser/Thr phosphatase that negatively regulates p53 and functions as an oncogenic driver. Its gene amplification and overexpression are frequently observed in various malignancies and disruption of PPM1D degradation has also been reported as a cause of cancer progression. However, the precise mechanisms regulating PPM1D stability remain to be elucidated.
View Article and Find Full Text PDFJ Biomed Sci
September 2025
Division of Gastroenterology, Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Oncometabolites are aberrant metabolic byproducts that arise from mutations in enzymes of the tricarboxylic acid (TCA) cycle or related metabolic pathways and play central roles in tumor progression and immune evasion. Among these, 2-hydroxyglutarate (2-HG), succinate, and fumarate are the most well-characterized, acting as competitive inhibitors of α-ketoglutarate-dependent dioxygenases to alter DNA and histone methylation, cellular differentiation, and hypoxia signaling. More recently, itaconate, an immunometabolite predominantly produced by activated macrophages, has been recognized for its dual roles in modulating inflammation and tumor immunity.
View Article and Find Full Text PDFMol Biotechnol
September 2025
Department of Biology, Faculty of Science, Marmara University, Göztepe, 34722, Istanbul, Türkiye.
Babesia bigemina, a tick-borne protozoan parasite, is one of the main causative agents of bovine babesiosis, a disease with significant economic impact on the cattle industry. One of the key enzymes involved in the parasite's metabolism is lactate dehydrogenase (LDH), which plays an essential role in the anaerobic glycolytic pathway by catalysing the conversion of pyruvate to lactate. In this study, B.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
September 2025
Inner Mongolia Medical University Affiliated Hospital, Hohhot, 010030, Inner Mongolia, China.
Purpose: Lung cancer is currently the most common malignant tumor worldwide and one of the leading causes of cancer-related deaths, posing a serious threat to human health. MicroRNAs (miRNAs) are a class of endogenous non-coding small RNA molecules that regulate gene expression and are involved in various biological processes associated with lung cancer. Understanding the mechanisms of lung carcinogenesis and detecting disease biomarkers may enable early diagnosis of lung cancer.
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