Int J Biol Sci. 2025 Jun 9;21(9):3949-3967. doi: 10.7150/ijbs.112645. eCollection 2025.

ABSTRACT

There is an urgent need for new therapeutic strategies against aggressive triple-negative breast cancer (TNBC), and drug repurposing offers a promising, time- and cost-effective solution. We previously reported that TGFβ leads to the tumorigenic role of NDRG1 in TNBC. Here, we aimed to identify drugs that mimic the transcriptomic signature after the inhibition of TGFβ-induced NDRG1 and to determine their antitumor properties. The transcriptomic signature was obtained by RNA sequencing after gene silencing of TGFβ-induced NDRG1 expression in TNBC cells. For the drug repositioning study, the transcriptome was further computationally analyzed by using the Connectivity Map tool. Efavirenz, ouabain, and vinburnine were selected as the repurposed drug candidates to evaluate their therapeutic potential in TNBC models as monotherapies and pairwise combinations. We determined that the candidate drugs significantly reduced tumor cell proliferation, cancer stem cells, self-renewal, clonogenic properties, and migration abilities in TNBC cell lines through the blockade of AKT. Importantly, we validated their translational potential in TNBC patient-derived xenograft organoids in combination with docetaxel. After validating that the drugs decreased p-AKT and Ki67, we demonstrated their antitumor activity in combination with docetaxel in organoids. In addition, drugs also showed efficacy in a docetaxel-resistant TNBC model, supporting their potential to overcome chemoresistance. In conclusion, these findings demonstrate the potential of efavirenz, ouabain, and vinburnine as repurposed agents capable of inhibiting TNBC cell proliferation, stemness, and migration. Their synergistic effects with docetaxel in organoid cultures further underscore their translational relevance and highlight a promising strategy for combination therapies to improve TNBC treatment.

PMID:40612674 | PMC:PMC12223764 | DOI:10.7150/ijbs.112645

J Mol Cell Cardiol Plus. 2025 Jun 16;13:100460. doi: 10.1016/j.jmccpl.2025.100460. eCollection 2025 Sep.

ABSTRACT

PURPOSE: Drug repurposing is a crucial strategy for researchers worldwide to accelerate drug development and mitigate associated risks and costs. Heart failure (HF) is a major global health problem with high prevalence and mortality rates. There are significant sex differences in HF, including in the risk factors and phenotype, which demand a sex-personalized drug treatment. A convenient approach in that direction is the reuse of drugs already approved for other conditions that are known to interact in sex-biased dysregulated pathways in HF. Numerous bioinformatics tools can help identify those candidates. This tutorial explores the utility of specific bioinformatics tools in identifying drugs to treat HF as a case study.

METHODS: Herein, we explain how NeDRex helps identify genes associated with disease and drug repurposing and how functional enrichment analysis can be performed with ShinyGO. We also explain how to predict targets of small bioactive molecules with SwissTargetPrediction and how to retrieve known and predicted interactions between chemicals and proteins with STITCH.

RESULTS: The tutorial demonstrates the use of these tools in searching for new HF treatments.

CONCLUSION: This tutorial is designed to ease entry into the utilization of the mentioned bioinformatics tools. This approach can also set a precedent for applying such tools to other diseases. The results presented in this tutorial are illustrative and do not constitute definitive evidence. They are intended for demonstration purposes only.

PMID:40612650 | PMC:PMC12221655 | DOI:10.1016/j.jmccpl.2025.100460

BMC Urol. 2025 Jul 4;25(1):154. doi: 10.1186/s12894-025-01837-0.

NO ABSTRACT

PMID:40611014 | DOI:10.1186/s12894-025-01837-0

Eur J Med Chem. 2025 Jun 28;297:117923. doi: 10.1016/j.ejmech.2025.117923. Online ahead of print.

ABSTRACT

The MST3 isozyme is integral to the modulation of cellular proliferation and apoptosis, with its dysregulation critically implicated in the tumorigenesis of high-grade neoplasms. Current investigations into MST3 inhibitors are in their initial stages, characterized by restricted structural diversity and suboptimal selectivity. Previous studies have shown that Riluzole and Ciprofloxacin have the potential to be repurposing into the tumor field. Notably, their hybridization may facilitate the formation of a continuous hydrogen bonding network between donor and acceptor moieties, thereby augmenting their applicability as novel kinase inhibitors. In this study, we designed and synthesized a series of Riluzole-Ciprofloxacin hybrids, subsequently identifying the lead compound LD-1 (GI50 = 683.1 nM in HepG2 cells) through an anti-proliferative screening process. Comprehensive kinase profiling and target inhibition assays revealed that LD-1 functions as a potent and selective inhibitor of MST3, exhibiting an IC50 value of 122.4 nM. Preliminary mechanistic studies indicated that LD-1 reduced the expression levels of cleaved caspase-3 and Bcl-2, resulted in inducing HepG2 cells apoptosis. Meanwhile, it decreased the expression level of cyclin B1 in a concentration-dependent manner, leading to cell cycle at the G2/M transition. The in vivo experiments demonstrated that LD-1 significantly suppressed tumor growth (TGI = 47.64 %) at a dosage of 40 mg/kg, coupled none obvious adverse reactions were observed. Collectively, LD-1, characterized by its novel structure, high potency, and selectivity as an MST3 inhibitor, showcases substantial potential for further investigation and therapeutic development.

PMID:40609223 | DOI:10.1016/j.ejmech.2025.117923

Bioinformatics. 2025 Jul 3:btaf353. doi: 10.1093/bioinformatics/btaf353. Online ahead of print.

ABSTRACT

SUMMARY: Understanding how small molecules perturb gene expression is critical for guiding drug discovery. We present DOSE-L1000-Viz, a Shiny application that facilitates comprehensive exploration of compound-induced transcriptomic responses across doses, time points, and cell types. Powered by a dose-response database, DOSE-L1000-Viz features interactive visualization, target-centric compound ranking based on efficacy and potency, and a signature search module using reference gene sets derived from generalized additive models. We benchmarked signatures derived from generalized additive models against traditional methods and demonstrated the utility of DOSE-L1000-Viz through use cases in transcription factor modulation and drug repurposing.

AVAILABILITY AND IMPLEMENTATION: DOSE-L1000-Viz and the backend data are publicly accessible at: https://dosel1000.com.All code is publicly hosted on GitHub (https://github.com/JmWangBio/DOSEL1000Viz) and archived via Zenodo (https://doi.org/10.5281/zenodo.15532392).

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40608961 | DOI:10.1093/bioinformatics/btaf353

Science. 2025 Jul 3;389(6755):eadt6736. doi: 10.1126/science.adt6736. Epub 2025 Jul 3.

ABSTRACT

The CRL4CRBN E3 ubiquitin ligase is the target of molecular glue degrader compounds that reprogram ligase specificity to induce the degradation of clinically relevant neosubstrate proteins. Known cereblon (CRBN) neosubstrates share a generalizable β-hairpin G-loop recognition motif that allows for the systematic exploration of the CRBN target space. Computational mining approaches using structure- and surface-based matchmaking algorithms predict more than 1600 CRBN-compatible G-loop proteins across the human proteome, including the newly discovered helical G-loop motif, and identify the noncanonical neosubstrate binding mode of VAV1 that engages CRBN through a molecular surface mimicry mechanism. This work broadens the CRBN target space, redefines rules for neosubstrate recognition, and establishes a platform for the elimination of challenging drug targets by repurposing CRL4CRBN through next-generation molecular glue degraders.

PMID:40608931 | DOI:10.1126/science.adt6736

Mol Divers. 2025 Jul 3. doi: 10.1007/s11030-025-11247-x. Online ahead of print.

ABSTRACT

Epidemic refers to a disease when the occurrence level exceeds expected standards (generating an epidemic phenomenon), in which infectious diseases pose a major challenge to global health. The concept of epidemiology arises with infectious diseases, which can infect many people within a certain period and lead to a pandemic. Especially in the face of sudden epidemics, time is of the essence. In such urgent scenarios, the time required for traditional drug discovery is often prohibitive, given its inherently long timelines, high costs, and frequent failures. Drug repurposing strategies, mainly divided into experimental and computational approaches,which involves identifying new therapeutic applications for already approved pharmaceuticals, have gained substantial attention as a time-efficient and cost-effective alternative. In light of this, the present review provides a comprehensive overview of the various approaches to drug repurposing for the treatment of emerging epidemic infectious diseases, the majority of which are sudden epidemics caused by viruses. In addition, we discuss the challenges faced by repurposing and propose innovative approaches to address these challenges to better achieve the successful translation of drug repurposing into clinical applications and maximize the therapeutic value of drugs.

PMID:40608229 | DOI:10.1007/s11030-025-11247-x

J Chem Inf Model. 2025 Jul 3. doi: 10.1021/acs.jcim.5c00689. Online ahead of print.

ABSTRACT

G protein-coupled receptors (GPCRs), the largest family of currently approved drug targets, are rarely targeted for cancer therapy. There is limited research on the role of GPCRs in pan-cancer, particularly regarding the underlying causes of their abnormal expression. The abnormal expression of GPCRs in tumors has generally been attributed to mutations and promoter methylation. However, transcriptional regulatory elements of GPCRs, such as G-quadruplexes (G4s), superenhancers (SEs), and mRNA structure, remain poorly understood. Then, these regulatory elements were explored by utilizing PRECOG, ROSE, and ViennaRNA algorithms. Meanwhile, cancer prognosis-related GPCRs were found based on different expression analyses and Cox regression. A total of 326 differentially expressed GPCRs were then identified, with 3,151 significant HR (hazard ratios) records in pan-cancer. Notably, most cancer prognosis-related GPCRs are coupled with Gi (GNAI1, GNAI2, and GNAI3) and Gq/11 signaling pathways. Moreover, G4s, SEs, and mRNA structure could be utilized to explain some of the abnormal expression for cancer prognosis-related GPCRs. Additionally, some of these GPCRs have known drug targets such as GCGR, CXCR4, GPR55, and so on. For an example of drug repurposing, four drugs (i.e., theophyline, caffeine, enprofylline, and flavone) were found that could be combined with immunotherapy for PAAD therapy patients. Finally, we developed GPCR-PCA (G protein-coupled receptors in pan-cancer), a web-based tool that provides fast, customizable queries based on our GPCR-related cancer analysis to facilitate clinical research targeting GPCRs. GPCR-PCA is available at http://gpcrpca.lsbz.store/.

PMID:40607519 | DOI:10.1021/acs.jcim.5c00689

Cancer Discov. 2025 Jul 3;15(7):1306-1308. doi: 10.1158/2159-8290.CD-25-0666.

ABSTRACT

The underlying genetic abnormalities that cause the phenotypic variation seen in patients with PTEN hamartoma tumor syndrome (PHTS) are poorly understood. In this issue, Castillo and colleagues report that the somatic loss of PTEN through copy-neutral loss of heterozygosity and the resulting uniparental disomy in endothelial cells lead to vascular malformations in PHTS, which respond to PI3K/AKT/mTOR pathway inhibitors. See related article by Castillo et al., p. 1350 .

PMID:40605508 | DOI:10.1158/2159-8290.CD-25-0666

Sci Rep. 2025 Jul 2;15(1):23626. doi: 10.1038/s41598-025-08148-2.

ABSTRACT

Npr1 is an essential protein in C. albicans, maintains ion homeostasis and nutrient transportation at cell membrane, and regulates the activity of ammonium transporter protein Mep2. Npr1 is one of the nine NPR/HAL family kinases classified under "Other groups" in C. albicans. In this study, we had performed protein homology modeling; structure based virtual screening of drugs, docking study and MD simulation. We employed drug repurposing pipeline from which 15 compounds were short listed. Among the compounds, Indacaterol was selected on the basis of high safety profile, binding affinity score value of - 9.3 kcal/mol, as well as its DFG-motif interaction. The best docked pose of the complex was utilized for MD simulation studies. The RMSD values from initial structure and protein-ligand complex were analyzed for the dynamic stability of drug-bound complex and compared with that of the apo-protein. The comparisons of average RMSF values show fluctuation within acceptable range, also very less change of Rg values occur between the protein and protein-ligand throughout the simulation. Further, the complex maintains on an average two hydrogen bonds throughout the simulation period. The binding stability of Npr1 and Indacaterol complex was also verified through Principal Component Analysis. The result secured from these computational approaches and techniques established that the drug has the potential to be developed as an anti-candida lead targeting candidiasis.

PMID:40603506 | DOI:10.1038/s41598-025-08148-2

ChemMedChem. 2025 Jul 2:e202500301. doi: 10.1002/cmdc.202500301. Online ahead of print.

ABSTRACT

Cationic ion channels are transmembrane proteins that regulate the flux of cations (potassium, sodium, and calcium) across cell membrane, playing a pivotal role in many cellular functions. Disruptions of their activity can lead to the so-called genetic or acquired channelopathies, a heterogeneous group of diseases that affect multiple human systems. Fenamates, a class of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), has recently emerged as modulators of cationic ion channels highlighting the possibility of their repurposing for the treatment ion channel-related disorders, such as channelopathies, chronic pain, epilepsy, cardiac arrhythmias and cancers. In this review, we describe the ability of fenamates (i.e. niflumic, flufenamic, mefenamic, meclofenamic and tolfenamic acids) to differentially modulate the activity of cationic ion channels. Overall, preclinical and clinical studies suggest that fenamates represent a promising class of compounds for drug repurposing and for the development of new molecules, offering novel therapeutic opportunities for patients affected by ion channel-related disorders.

PMID:40600901 | DOI:10.1002/cmdc.202500301

Curr Cancer Drug Targets. 2025 Jun 23. doi: 10.2174/0115680096372733250611114329. Online ahead of print.

ABSTRACT

Cancer is a major health problem and the second leading cause of death worldwide. Chemotherapy remains the mainstay therapeutic option to treat cancer patients, which consists of conventional, hormonal, and/or targeted therapies. However, the significant adverse effects, negative impact on patients' quality of life, and high costs of some medications, as well as the challenges associated with developing new drugs, are prompting the scientific community to seek innovative and alternative treatment strategies. One such strategy is drug repurposing, the use of existing drugs, already approved for other medical conditions for cancer treatment, lev-eraging their known safety and toxicity profiles. Among these groups are the selective seroto-nin reuptake inhibitors (SSRIs) that target serotonin transporter (SERT). In this review, we presented the mechanism of action of SSRIs on the systems biology level, along with their network pharmacology related to protein-protein interactions. We also showed the association of SSRIs and SERT with various diseases, including several types of cancer. Knowing the expression of SERT in cancer and being a target for SSRIs, studies have been investigating the repurposing of SSRIs for cancer treatment. This review also presents a summary of several clinical and preclinical studies that have investigated the use of SSRIs either as single agents or in combination with conventional chemotherapy for cancer treatment, showing promising results. Collectively, they have shown the antiproliferative and growth inhibition effects on cancer cells and/or tumors. We also presented the mechanism(s) of action and pathways these drugs are acting in cancer, along with molecular changes in cellular proteins and enzymes.

PMID:40600564 | DOI:10.2174/0115680096372733250611114329

Curr Pharm Biotechnol. 2025 Jun 23. doi: 10.2174/0113892010371761250616112614. Online ahead of print.

ABSTRACT

Rare diseases, defined as conditions affecting fewer than 200,000 people in the United States or less than 1 in 2,000 people in Europe, pose significant challenges for healthcare systems and pharmaceutical research. This comprehensive review examines the evolving landscape of orphan drug development, analyzing scientific, economic, and regulatory challenges while highlighting recent technological breakthroughs and innovative approaches. We explore how artificial intelligence, next-generation sequencing, and personalized medicine are revolutionizing rare disease research and treatment development. The review details key advances in therapeutic approaches, including gene therapy, cell-based treatments, and drug repurposing strategies, which have led to breakthrough treatments for previously untreatable conditions. We analyze the impact of international collaborations, such as the International Rare Diseases Research Consortium, and discuss how regulatory frameworks worldwide have evolved to accelerate orphan drug development. The paper highlights the growing market for orphan drugs, projected to reach $242 billion by 2024 while examining the complex challenges of ensuring treatment accessibility and economic sustainability. We assess innovative clinical trial designs, patient registry development, and emerging strategies in personalized medicine that are transforming the field. Despite notable advancements, significant gaps remain in diagnosis, treatment accessibility, and sustainable funding for rare disease research. The review concludes by proposing specific actions for enhancing international collaboration, improving patient registries, and aligning incentives to address the unmet medical needs of rare disease patients, emphasizing the critical role of continued public-private partnerships and technological innovation in advancing orphan drug development.

PMID:40600560 | DOI:10.2174/0113892010371761250616112614

Sci Rep. 2025 Jul 1;15(1):20560. doi: 10.1038/s41598-025-05054-5.

ABSTRACT

GBM is one of the most aggressive malignancies, having the greatest fatality rate and average life years lost. The current standard medicine, temozolomide (TMZ), is ineffective, requiring the development of new treatments. However, identifying and introducing a novel medicine takes time and money. In this context, repurposing FDA-approved drugs can be a novel yet efficient alternative method. Here, we, therefore, investigated the differential expression signatures of genes of patients suffering from GBM from publicly available GEO datasets and constructed a connectivity map. Functional annotation and KEGG pathway analysis showed dysregulated molecular activities and pathways. Based on their gene ontologies, putative key genes and hub genes linked with the disease were identified, and the C-MAP database was scanned for FDA-approved medicinal compounds that could alter hub gene expression or associated pathways. Our in-silico investigation showed that Gemfibrozil (Gem) and Doxylamine (Doxy) might reverse GBM disease patterns by deregulating GBM-related genes. Evaluation of the GBM inhibitory potential of these drugs through in-vitro and three-dimensional spheroid assay showed promising results. These drugs were more cytotoxic than TMZ; however, they synergised with TMZ as well. Interestingly, the cellular homeostatic process autophagy which has been implicated significantly in GBM pathogenesis and therapy resistance, was found to be inhibited by the drugs Gemfibrozil and Doxylamine, signifying their prospective potential. Therefore, in this study, we, for the first time, identify drugs with the ability to cross the blood brain barrier (BBB), with potential cytotoxic effects beyond TMZ, and with autophagy inhibitory potential, which can be further explored for repurposing against GBM.

PMID:40595852 | DOI:10.1038/s41598-025-05054-5

Sci Rep. 2025 Jul 1;15(1):22331. doi: 10.1038/s41598-025-07989-1.

ABSTRACT

Abdominal aortic aneurysm (AAA) is a non-communicable disease (NCD) with high morbidity and mortality, commonly observed worldwide. Understanding its molecular mechanisms and identifying potential therapeutic targets are crucial for disease screening, diagnosis, and treatment. In this study, we conducted a meta-analysis of multiple genome-wide association studies (GWASs) to identify genetic variants associated with AAA and explored the functional implications of these variants in disease pathology. We identified differentially expressed genes (DEGs) based on significant single nucleotide polymorphisms (SNPs) from expression quantitative trait loci (eQTL) and transcriptome-wide association study (TWAS) analyses. Using these DEGs, we constructed an AAA-related protein-protein interaction (PPI) network and prioritized key genes for further analysis. Furthermore, we performed drug repurposing by identifying drug-gene and drug-protein interactions in existing databases and validated potential candidates through molecular docking. Our findings reveal 42 novel disease-associated SNPs and 52 previously unreported disease-related genes. Some residual confounding factors cannot be fully ruled out and may represent a limitation of our study. However, it is worth noting that only a minority of SNPs exhibited heterogeneity. Functional pathways analysis highlighted key processes, including lipid and cholesterol metabolism, tissue remodeling, and acetylcholine activation. We identified 74 DEGs through eQTL and TWAS analyses, with PPI network analysis highlighting CD40 and LRP1 as key proteins. Drug repurposing and molecular docking suggested abciximab and paclitaxel as potential therapeutic agents targeting CD40, while ivermectin emerged as a strong candidate for LRP1 binding. In conclusion, our integrative bioinformatics frameworks links genomics and transcriptomics with network biology and structural modeling, providing valuable insights into the molecular mechanisms of AAA and potential therapeutic strategies.

PMID:40595262 | DOI:10.1038/s41598-025-07989-1

Sci Rep. 2025 Jul 1;15(1):21171. doi: 10.1038/s41598-025-07751-7.

ABSTRACT

The rising prevalence and rapid spread of multidrug-resistant bacteria have resulted in ineffective treatments, impacting millions of lives globally. In response to these challenges, drug repurposing has garnered attention as a viable alternative to traditional drug discovery and development processes. This study aimed to investigate the synergistic effects of dimetridazole and cefotaxime by evaluating their efficacy against E. coli. A checkerboard assay was performed to examine the synergy of dimetridazole in combination with cefotaxime against drug-resistant E. coli NX400. The results showed synergistic effects. Additionally, a growth curve was used to assess the growth inhibitory effects. Membrane permeability and membrane integrity were evaluated using fluorescence microscopy and scanning electron microscopy. We also analyzed the composition of membrane fatty acids and the expression of fatty acid biosynthesis-related genes. Finally, a Galleria mellonella infection model was employed to evaluate the synergistic antibacterial activity. The results showed that dimetridazole in combination with cefotaxime had significant antibacterial activity against MDR E. coli. This finding was confirmed by an in vivo G. mellonella larval infection model, in which dimetridazole revived the activity of cefotaxime. The antibacterial mechanisms are related to the bacterial membrane. Combination of dimetridazole and cefotaxime disrupts membrane integrity, permeability, and biosynthesis.

PMID:40594620 | DOI:10.1038/s41598-025-07751-7

Sci Rep. 2025 Jul 1;15(1):22382. doi: 10.1038/s41598-025-05013-0.

ABSTRACT

Ovarian cancer (OvCa) is the sixth most common gynaecological cancer in the UK, accounting for over 200,000 deaths worldwide. Cancerous Inhibitor of Phosphatase 2 A (CIP2A) is an oncoprotein and an endogenous inhibitor of PP2A. CIP2A is a key regulator for cellular processes (e.g. proliferation, DNA damage) and is involved in the progression of many malignancies. In this study we provide a comprehensive overview of its role in OvCa making use of in silico tools, clinical samples and in vitro models. CIP2A is overexpressed in OvCa patients, with metastatic patients having significantly higher expression when compared to patients with malignant and benign ovarian tumours. High CIP2A expression reduces both overall-and progression-free survival, whereas an R530T mutation is predicted to cause structural destabilisation of the CIP2A dimer. We also provide evidence for microRNA (miRNA) and mRNA target interactions with CIP2A. Finally, we have studied the effects of CIP2A inhibition in an in vitro BRCA2 model compared to BRCA2 wild-type OvCa cells, using RNA-sequencing. Gene enrichment pointed towards changes p53 pathway, protein metabolism, transporter activity, DNA replication, and cell cycle. Our data provide a novel insight into the role of CIP2A in OvCa and the potential of drug repurposing for therapeutic interventions.

PMID:40594400 | DOI:10.1038/s41598-025-05013-0

Sci Rep. 2025 Jul 2;15(1):22881. doi: 10.1038/s41598-025-05715-5.

ABSTRACT

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a significant challenge in oncology despite advances in targeted and immune-based therapies. NSCLC accounts for approximately 85% of all lung cancer cases, with five-year survival rates ranging from 4 to 17%, depending on disease stage and regional factors. Chemotherapy resistance remains a major hurdle, contributing to poor patient prognosis. This study explores the therapeutic potential of Sd-021, a novel decursinol derivative, compared to its parent compound, decursin, within various NSCLC cell lines. Our results reveal that Sd-021 demonstrates enhanced anticancer activity, highlighted by a more significant reduction in cell viability, increased induction of apoptosis, and more pronounced cell cycle arrest. Notably, Sd-021 shows increased inhibition of the EGFR/STAT3 signaling pathway in EGFR wild-type cell lines, including A549, H460, and H1299 cells. Moreover, in vivo experiments employing a subcutaneous xenograft mouse model reveal that Sd-021 reduces tumor volume with minimal systemic toxicity, as indicated by histopathological assessments revealing reduced tumor proliferation and heightened apoptosis. The minimal toxicity of Sd-021 offers reassurance regarding its safety for potential clinical applications. In conclusion, these findings highlight the promise of Sd-021 as a therapeutic agent against NSCLC.

PMID:40594251 | DOI:10.1038/s41598-025-05715-5

Sci Rep. 2025 Jul 1;15(1):21211. doi: 10.1038/s41598-025-01448-7.

ABSTRACT

The exact cause of psoriasis is still unclear and there is no treatment available for its permanent reemission. The available biologics for disease treatment, are stated to be associated with a high cost of treatment, a significantly increased risk of serious infections, and have also been reported to show major contradictions in patients with tuberculosis and cardiovascular disorders. Therefore, drug repurposing could be an appealing strategy to find novel treatments for psoriasis, saving time, cost and with viable chance of success. The goal of the present study was to identify the FDA approved drugs which can be proposed as potential anti-psoriasis drugs. The known drug target interactions of 19 autoimmune diseases, 4 cardiovascular risk factors, and each of infectious, lung, and mood disorders were retrieved using various public databases, i.e., DrugBank, PharmGKB, clinicaltrial.gov database, TTD, CTD, and the Unified Medical Language System NDF-RT. The drug target interaction of prioritised drugs, obtained using molecular function GO mappings from the QuickGO database through NBI score was analysed using a molecular docking approach. Further, one-SVM algorithm prediction was done to validate the docking outcome and molecular dynamics simulation of top drug-target molecule was performed to propose potential anti-psoriasis drugs. The study identified Pioglitazone, Trimipramine and Dimetindene as top three contender amongst many other drugs as a new indication against psoriasis.

PMID:40593806 | DOI:10.1038/s41598-025-01448-7

Results Probl Cell Differ. 2025;75:309-328. doi: 10.1007/978-3-031-91459-1_11.

ABSTRACT

Histone deacetylase inhibitors (HDACi) have gained attention for their potential therapeutic effects in various immune-related diseases and solid organ transplantation. This review focuses on the role of HDACs' expression in immune responses, especially of T and B cells, in organ transplant rejection. We examined the expression levels of HDACs in T and B cells across different immune states, providing insight into their regulatory functions during immune activation and tolerance. Through an analysis of in vitro, in vivo, and preclinical studies, we explored the effects of HDACi on immune modulation, highlighting their impact on T- and B-cell function in diseases other than cancer. Finally, we discussed the outcomes of HDACi treatment in various organ transplantation models, assessing their potential to mitigate rejection, promote tolerance, and improve graft survival. The review synthesizes current evidence, identifies knowledge gaps, and offers a comprehensive outlook on HDACi for clinical applications in organ transplantation.

PMID:40593215 | DOI:10.1007/978-3-031-91459-1_11