In silico pharmacology最新文献

{"title":"In silico insights into shared molecular mechanisms and drug repurposing for non‑small cell lung cancer and tuberculosis.","authors":"Nazia Zarin, Nafis Fuad Shahir, Tasnim Hosen Tanha, Mimuna Nishad, Shaila Haque, Md Enamul Kabir Talukder, Tanzil Zahan","doi":"10.1007/s40203-026-00767-5","DOIUrl":"10.1007/s40203-026-00767-5","url":null,"abstract":"<p><p>Non‑small cell lung cancer (NSCLC) and tuberculosis (TB) represent major global health burdens, with evidence of a molecular interconnection. To understand their shared mechanisms, we integrated three NSCLC and two TB RNA‑seq datasets and identified 33 common differentially expressed genes (cDEGs). Enrichment analyses, protein-protein interaction (PPI) network mapping, cancer‑specific validations, and survival analyses were performed on all cDEGs. The PPI network highlighted <i>KIF18A, ANLN, TLR4, EPAS1</i>, and <i>DLC1</i> as central hub genes, with enrichment pointing to immune‑inflammatory signaling, epithelial remodeling, and cell‑cycle regulation as key processes underlying NSCLC-TB comorbidity. Profiling of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), accounting for about 80% of NSCLC, showed <i>KIF18A, ANLN, STIL</i>, and <i>GALNT14</i> overexpression linked to advanced stage and poor survival, with 4-14% alterations mainly from mRNA upregulation. Leveraging their network centrality and prognostic significance, KIF18A and ANLN were selected as receptor targets for structure‑based drug screening. A library of 213 anti‑NSCLC, anti‑TB, and antimicrobial compounds was screened against these targets using AutoDock and Glide, followed by pharmacokinetic and toxicity assessment. Levofloxacin (targeting ANLN) and Capmatinib (targeting KIF18A) exhibited the most favorable docking scores and ADME/Tox profiles, with stable binding modes, favorable MM-GBSA binding free energies, and refined dynamic cross-correlation and free-energy landscapes over 100 ns molecular dynamics simulations, nominating them as promising in silico predicted drug agents relevant to both NSCLC and TB. Our in silico transcriptomic and structural‑dynamics analysis reveals shared infection-cancer mechanisms and identifies candidate therapeutics for further evaluation.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00767-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"260"},"PeriodicalIF":0.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and synthesis of novel benzothiazole-pyrazole derivatives: cytotoxicity against panc-1 cancer cells and EGFR, antioxidant activity, molecular docking, MD simulations, ADMET, and DFT analysis.","authors":"Ahmed A Waleed, Hamid H Mohammed, Najim A Al-Masoudi, Yahia Bekkar, Lanez Elhafnaoui, Dalal Harkati","doi":"10.1007/s40203-026-00737-x","DOIUrl":"10.1007/s40203-026-00737-x","url":null,"abstract":"<p><p>A new benzothiazole-based pyrazole-imine derivatives <b>10</b> and <b>11</b> were prepared from 6-methoxy-1,3-benzothiazole-2-amine (<b>4</b>) through successive multi-steps synthesis. Biological evaluation demonstrated that compound <b>11</b> exhibited notable antiproliferative activity against Panc-1 cancer cells (IC₅₀ = 93.4 µM), while exhibiting lower cytotoxicity toward healthy HDFn cells (IC₅₀ = 213.2 µM). Additionally, compound <b>11</b> displayed significant antioxidant activity, with 92.79% DPPH radical-scavenging activity at 100 µg/mL, comparable to ascorbic acid (95%). Molecular docking predicted favorable binding of compound <b>11</b> to GPR119, human ribonucleotide reductase, and RIP1 protein kinase, while ADMET, DFT, MEP, ELF/LOL, and RDG/NCI analyses provided complementary insights into its physicochemical properties, electronic characteristics, and protein-ligand interactions. Molecular dynamics simulations over 100 ns further supported the stability of the selected protein-ligand complexes. Overall, these experimental and computational findings identify compound <b>11</b> as a promising lead compound for further optimization and experimental validation as a potential antiproliferative and antioxidant agent.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00737-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"261"},"PeriodicalIF":0.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational identification of phytochemical NMDAR pore-targeting candidates for radiation-induced cognitive decline.","authors":"Jemema Agnes Tripena Raj, Abhishek Chatterjee, Nikhil Gadewal, Jayant S Goda","doi":"10.1007/s40203-026-00763-9","DOIUrl":"10.1007/s40203-026-00763-9","url":null,"abstract":"<p><p>Radiation-induced cognitive decline (RICD) is a major late complication of cranial radiotherapy, particularly in pediatric brain tumor survivors. Memantine, an uncompetitive <i>N</i>-methyl-D-aspartate receptor (NMDAR) channel blocker, provides clinically relevant neuroprotection, However, the development of additional NMDAR-targeting candidates with favorable CNS penetration and pharmacological properties remains an unmet need. An integrated computational workflow was used to prioritize phytochemical NMDAR pore-targeting candidates. The memantine-bound NMDAR structure (PDB ID: 7SAD) guided pharmacophore modeling and virtual screening of 17,967 IMPPAT phytochemicals, followed by drug-likeness and CNS pharmacokinetic filtering. Prioritized compounds were evaluated by molecular docking, MM-GBSA/MM-PBSA, triplicate membrane-embedded molecular dynamics (MD), residue-contact and pore-geometry analyses, PCA/FEL, DFT, and in silico toxicity prediction. Filtering yielded 14,491 drug-like compounds, 1429 pharmacophore hits, 77 docking/MM-GBSA candidates, and seven compounds for detailed analysis. Triplicate 100 ns membrane simulations revealed ligand-dependent differences in binding energetics, interaction persistence, conformational sampling, and pore geometry. Dehydrocrenatidine (IMPHY010917), Skimmianine (IMPHY007265), Dehydrocrenatine (IMPHY007797), and Vasicinol (IMPHY004852) showed the most compelling complementary profiles, although no single compound consistently ranked highest across all descriptors. Dehydrocrenatidine, Skimmianine, Dehydrocrenatine, and Vasicinol are prioritized as putative NMDAR pore-targeting phytochemicals for RICD. Their complementary energetic, interaction, and conformational profiles provide a basis for experimental evaluation of NMDAR inhibition, CNS exposure, and radiation-relevant neuroprotection.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00763-9.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"258"},"PeriodicalIF":0.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular recognition of axonal injury-associated candidate hub genes and predicted inhibitors across Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.","authors":"Ayesha Naseer, Naveed Iqbal, Ishrat Bibi, Syed Ali Raza Shah, Misbah Khalid, Ayesha Khalid","doi":"10.1007/s40203-026-00774-6","DOIUrl":"10.1007/s40203-026-00774-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) have converging molecular pathologies such as neuroinflammation, mitochondrial dysfunction, and axonal degeneration, but do not have broadly effective disease-modifying therapies. A novel computational strategy was used in this study with an integrated in-silico pipeline to determine common candidate hub genes across AD, PD, and ALS and to computationally screen candidate inhibitors. The gene expression datasets were retrieved from the Gene Expression Omnibus database and analyzed with limma R package for blood-derived gene expression datasets for AD (GSE63060), PD (GSE99039) and ALS (GSE112680). A multi-dataset intersection analysis revealed 138 genes commonly upregulated and 0 commonly downregulated genes, which were functionally enriched in immune regulation, apoptotic signaling and mitochondrial instability pathways. Protein-protein interaction network analysis identified three key genes (MMP9, PTPN6 and TNFRSF1A) as high-confidence candidate hub genes for AD, PD, and ALS. The ZINC library of 34,853 compounds was screened for drug-like properties using QikProp to yield 16,466 drug-like compounds. Based on the comparative screening results, the structure of MMP9 (PDB ID: 8K5Y) was chosen for further analysis and two of the selected compounds ZINC04582833, ZINC00047690 were identified as the two highest ranked compounds with docking scores of - 10.4 and - 9.7 kcal/mol respectively. Both complexes were further evaluated by 100 ns MD simulations, showing RMSD profile stability, maintained secondary structure for both complexes. The results in this study make ZINC04582833 and ZINC00047690 computationally prioritized candidates for shared neurodegenerative targets for experimental validation.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00774-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"259"},"PeriodicalIF":0.0,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering potent natural products against Sars-Cov-2 main protease using structure-based virtual screening and simulation studies.","authors":"Pawan Gupta, Vishnu Kumar Sharma","doi":"10.1007/s40203-026-00759-5","DOIUrl":"https://doi.org/10.1007/s40203-026-00759-5","url":null,"abstract":"<p><p>The aim of the studies is to perform structure-based virtual screening against the main protease (Mpro) of SARS-CoV-2 to identify the novel natural product using in silico methods. The screening studies ranked the first 10 screened molecules in the docking method along with marketed drugs (<b>NTR</b> and <b>LPV</b>) and a known inhibitor (<b>D95</b>). These 10 molecules exhibited satisfactory ADME results. The stability studies using these 10 molecules were performed till 100 ns and extended three times using the MD simulation method. The triplicate MD simulation (three replicates) studies were found to have satisfactory stability parameters for the <b>F35</b>, like RMSD, RMSF, Rg, etc. The PCA demonstrated three replicates of the <b>X77</b> and <b>NTR</b> displayed the substantial reproducible essential dynamics and stable conformational behaviour throughout the MD simulation. However, the <b>F35</b> complex also followed the considerable overlap in motion or compact conformational sampling during MD simulation. Moreover, the zero-energy state structure of Mpro on the free energy landscape plot suggested that the novel natural product <b>F35</b> also performed satisfactorily as compared to the known inhibitors (<b>NTR</b>, <b>LPV</b>, <b>X77</b>). Moreover, extended MD simulation was found that <b>F35</b> is having binding potential similar to <b>X77</b> (<b>NTR </b>> <b>F35 </b>≈ <b>X77)</b> but need to be proved biologically using different in vitro/in vivo experiments. The <b>F35</b> is a novel natural product never reported against Mpro SARS-CoV-2 to date. These computational studies suggested that the natural product-<b>F35</b> (plant: <i>Ornithogalum caudatum</i>) followed the similar binding patterns and binding energy among the known Mpro inhibitors. Thus, <b>F35</b> could be an alternative and complementary therapy against SARS-CoV-2 infection and exploited further for designing and searching for novel Mpro inhibitors.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00759-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"257"},"PeriodicalIF":0.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing for psoriasis: virtual screening, molecular dynamics, and ADMET profiling for the identification of potential DHFR inhibitors.","authors":"Sadaf Naeem, Syeda Zoya Mahmood, Subohi Noorulain, Bisma Shahid","doi":"10.1007/s40203-026-00761-x","DOIUrl":"10.1007/s40203-026-00761-x","url":null,"abstract":"<p><p>Psoriasis is a chronic dermatological disorder affecting approximately 43 million people globally, with current treatments limited by toxicity and high costs. Dihydrofolate reductase (DHFR), a crucial enzyme in folate metabolism essential for DNA synthesis, represents a validated therapeutic target for psoriasis. This study aimed to identify FDA-approved drugs with potential DHFR inhibitory activity using an integrated computational approach combining molecular docking, ADMET prediction, and molecular dynamics simulations. A total of 2311 FDA-approved drugs from DrugBank were docked against human DHFR (PDB ID: 1S3V). Ten compounds exhibited strong binding affinities (MolDock scores: -209.9 to -261.3 kcal/mol), with Velpatasvir showing the highest score (-261.3 kcal/mol), followed by Ledipasvir (-242.4 kcal/mol). ADMET profiling classified both compounds as Medium Priority. To evaluate binding stability, 20 ns triplicate MD simulations and MM-GBSA calculations were performed. Both compounds formed stable complexes, with mean protein RMSD values of 2.36 ± 0.10 Å (Velpatasvir) and 2.37 ± 0.26 Å (Ledipasvir). Velpatasvir demonstrated more consistent binding across replicates (RMSF: 2.79 ± 1.65 Å; MM-GBSA SD: 5.52 kcal/mol) compared to Ledipasvir (RMSF: 6.22 ± 2.12 Å; MM-GBSA SD: 13.01 kcal/mol). PCA and DCCM analyses revealed that Velpatasvir induced highly consistent motion patterns, while Ledipasvir exhibited more variable conformational sampling. Both compounds showed favourable binding free energies (Velpatasvir: -43.39 ± 5.52 kcal/mol; Ledipasvir: -49.19 ± 13.01 kcal/mol). These findings suggest Velpatasvir and Ledipasvir as promising DHFR inhibitors warranting experimental validation, and demonstrate drug repurposing as a cost-effective strategy for discovering novel psoriasis therapies.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00761-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"256"},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating network pharmacology to investigate the mechanism of esculetin from <i>Nyctanthes arbor-tristis</i> leaves against breast cancer.","authors":"Rohit Singh Negi, Nitish Kumar, Rakesh Kumar Gupta, Jyotirmayee Behera, Manjeet Kumar Sah Gond, Pawan Kumar Dubey, Sunil Kumar Mishra","doi":"10.1007/s40203-026-00765-7","DOIUrl":"10.1007/s40203-026-00765-7","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The development of efficient treatment medicines with multitarget modes of action is necessary because breast cancer continues to be one of the leading causes of cancer-related mortality among women worldwide. Although esculetin (6,7-dihydroxycoumarin), a naturally occurring phenolic compound, has demonstrated promising anticancer activity, its molecular mechanism against breast cancer remains poorly understood. Therefore, this study aimed to investigate the therapeutic potential and underlying molecular mechanisms of esculetin against breast cancer using an integrated computational and experimental approach. We employed an integrated strategy that combined network pharmacology, density functional theory (DFT), molecular docking, molecular dynamics (MD) simulations, and experimental validation on MCF-7 cells. Firstly, we retrieved potential esculetin targets and breast cancer targets from multiple databases to identify overlapping targets. Later, we performed protein-protein interaction (PPI) network analysis and pathway enrichment analyses to identify key targets and associated signaling pathways. The electronic properties of esculetin were evaluated using DFT analysis. At the same time, molecular docking and simulations were conducted to assess protein-ligand interactions and complex stability, followed by MM-PBSA to determine the total energy. Lastly, experimental validation was performed in MCF-7 breast cancer cells using cell viability, live/dead, and reactive oxygen species (ROS) assays. A total of 591 overlapping targets were identified between esculetin and breast cancer. PPI network analysis highlighted EGFR, ERBB2, JAK2, PIK3CA, and PTPN11 as key hub targets. Pathway enrichment analyses indicated significant involvement of ERBB2-associated signaling pathways, including PI3K/AKT, SHP2, MAPK, and EGFR. DFT analysis demonstrated favorable electronic properties, supporting the molecular reactivity of esculetin. Molecular docking revealed that esculetin exhibits moderate binding affinities toward the identified hub protein ERBB2, while molecular simulation showed the structural stability of the esculetin-ERBB2 complex throughout the simulation. In vitro studies showed that esculetin reduced cell viability at 160 μM in MCF-7 cells, induced intracellular ROS accumulation, and promoted cell death as confirmed by AO/PI staining. Overall, this study provides a computationally informed framework for understanding the potential anticancer activity of esculetin in breast cancer. The predicted interaction between ERBB2 and the associated EGFR/ERBB2-PI3K/MAPK signaling network suggests a putative mechanism that warrants experimental validation. The findings, therefore, provide a basis for future target-specific and in vivo studies to establish the molecular relevance and therapeutic potential of esculetin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Graphical abstract: &lt;/strong&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Supplementary information: &lt;/strong&gt;The online version contains supplementary mater","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"255"},"PeriodicalIF":0.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149129175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring cheminformatics tools to combat prostate cancer: diagnostics, therapeutics, and mechanistic studies.","authors":"Samuel Igwe, Cyril Osereme Ehi-Eromosele, Inemesit Asukwo Udofia, Oluwakemi Adekunbi Oloba-Whenu","doi":"10.1007/s40203-026-00762-w","DOIUrl":"https://doi.org/10.1007/s40203-026-00762-w","url":null,"abstract":"<p><p>Despite recent progress, prostate cancer (PCa) remains one of the most prevalent forms of cancer in men worldwide, and a variety of challenges remain to prevent timely detection, biomarker specificity, and the development of treatment resistance due to tumor heterogeneity and changes in androgen receptor (AR) signaling. For PCa diagnosis, treatment, and mechanistic research, cheminformatics and bioinformatics tools like virtual screening, molecular docking, pharmacophore modeling, and QSAR modeling, computational drug repurposing, molecular dynamics simulation, network pharmacology, multi-omics profiling, and MRI/radiomics are viewed as an interconnected continuum, with AI/ML/DL as a common analytical layer. To distinguish between clinically useful diagnostic methods and discovery-stage computational methods, a comparative evaluation methodology is presented that assesses each method according to several criteria: clinical maturity, predictive value, validation requirements, and clinical translatability. In addition to MRI, the only clinically validated modality described, other virtual screening, docking, QSAR, and network pharmacology techniques are predominantly used for discovery and preclinical applications and must be further validated through experimental and prospective clinical studies before becoming translatable to clinical use. Although multi-omics and network pharmacology methods are used to gain mechanistic insights into resistance pathways, cheminformatics-based strategies have helped identify candidate compounds and repurpose drugs targeting AR- and CRPC-related targets. Aside from diagnostic classification, AI/ML/DL applications currently being developed involve multimodal integration, biomarker discovery, and patient stratification, yet to be adopted in clinical practice, there is a need for explainable AI and multi-cohort prospective validation. An integrated computational pathway from discovery to experimental and clinical validation is suggested to facilitate future translational efforts. These computational tools together show great promise for improving the precision of PCa management, but require proper, sequential experimental and clinical evaluation of their in-silico predictions.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"254"},"PeriodicalIF":0.0,"publicationDate":"2026-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics-based identification of capsaicin target genes associated with trastuzumab resistance in HER2-positive breast cancer: in silico and qRT-PCR validation studies.","authors":"Adam Hermawan, Dyaningtyas Dewi Pamungkas Putri, Dini Maharani, Nurul Fatimah, I Made Rhamandana Putra, Intan Ayu Lestari, Chris Djerico, Monica Hana Widyardhita, Wasita Rachma Widayanti","doi":"10.1007/s40203-026-00753-x","DOIUrl":"https://doi.org/10.1007/s40203-026-00753-x","url":null,"abstract":"<p><p>Trastuzumab (TRZ) is a primary treatment for HER2-positive (HER2+) breast cancer, but its effectiveness is often limited by drug resistance linked to the PI3K signaling pathway. Capsaicin (CAP), a natural compound from chili peppers, has been shown to block the PI3K/AKT pathway. This study aimed to computationally identify specific gene targets of CAP and clarify its molecular mechanism for overcoming TRZ resistance. Computational analyses was conducted to identify potential capsaicin targets (PTCT), continued the in vitro assay on on TRZ-resistant HCC1954 breast cancer cells including cytotoxicity, cell cycle progression, and mRNA expression levels. We identified 54 genes as PTCT and selected ten as hub genes: <i>EGFR, VEGFA, SRC, TIMP1, FOS, CCND1, TGFB1, ICAM1, EDN1,</i> and <i>PPARA</i>. The combination of CAP and TRZ demonstrated a strong synergistic cytotoxic effect, with a significantly lower IC₅₀ of 3.78 μM compared to 418 μM for CAP alone, confirmed as synergistic by Combination Index analysis (CI = 0.06-0.36), and significantly increase in the Selectivity Index (SI) value to 39.4; an increase in the S and G2/M population, and upregulated the mRNA levels of most hub genes while downregulating <i>SRC</i> and <i>EDN1</i>. In conclusion, CAP effectively reverses TRZ resistance by modulating cell cycle and the transcriptional of specific hub genes. Further research should focus on elucidating the precise molecular mechanisms.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00753-x.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"253"},"PeriodicalIF":0.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149120674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and immunomodulatory activities of a peptide-rich preparation from <i>Adenanthera pavonina</i> seeds against multidrug-resistant β-haemolytic <i>Staphylococcus aureus</i>.","authors":"Olumide Oluyele, Temitayo Benedict Ibitoye","doi":"10.1007/s40203-026-00757-7","DOIUrl":"10.1007/s40203-026-00757-7","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> (<i>S. aureus</i>) is notorious for antibiotic resistance and invasive infections. This study evaluated the antimicrobial and immunomodulatory properties of peptide-rich preparation from <i>Adenanthera pavonina</i> seeds (APSP) against multidrug-resistant β-haemolytic <i>S. aureus</i>. APSP was extracted using standard procedures, and its antimicrobial activity was evaluated using agar-well diffusion and killing kinetics assays. High-performance liquid chromatography identified its constituent amino acids, which were subjected to molecular docking against DNA gyrase B. The therapeutic effects of APSP were evaluated in vivo in seven groups (<i>n</i> = 4) of <i>S. aureus</i>-infected and APSP-treated Wistar rats. HPLC analysis identified arginine, proline, alanine, methionine, histidine, and isoleucine among the constituents. APSP demonstrated strong antimicrobial activity, producing a 22 mm inhibition zone at 100 mg/mL and a minimum inhibitory concentration of 25 mg/mL, with time-dependent reduction in bacterial counts. In vivo, APSP alleviated infection-associated symptoms and modulated PCV, WBC, and lymphocyte counts, particularly at 50 mg/kg. It also reduced ALT and AST levels without significant changes in ALP, while enhancing IgM and IgG responses. Additionally, APSP increased IFN-γ levels and modulated TNF-α and IL-6 in a dose-dependent manner. Overall, APSP demonstrated antimicrobial and immunomodulatory activities against multidrug-resistant <i>S. aureus</i>, supporting its potential as a candidate for further investigation in the management of infections caused by multidrug-resistant <i>S. aureus</i>.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00757-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 3","pages":"252"},"PeriodicalIF":0.0,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149076978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}