In silico pharmacology最新文献

{"title":"Integrated data mining, network pharmacology and molecular docking to explore the medication rules and mechanism of traditional Chinese medicine compound in the treatment of acne.","authors":"Wanyun Zhu, Ziyan Cheng, Qimei Xie, Bin Sun, Min Wei, Songfeng Wang, Yiyun Qian, Pingping Song","doi":"10.1007/s40203-026-00702-8","DOIUrl":"10.1007/s40203-026-00702-8","url":null,"abstract":"<p><p>Through data mining of traditional Chinese medicine (TCM) formulas for acne, high-frequency herbs were identified, including <i>Glycyrrhizae Radix et Rhizoma</i> (gancao, GC)<i>, Scutellariae Radix</i> (huangqin, HQ)<i>, Lonicerae Japonicae Flos</i> (jinyinhua, JYH)<i>, Salviae Miltiorrhizae Radix et Rhizoma</i> (danshen, DS)<i>, and Paeoniae Radix Rubra</i> (chishao, CS). These herbs collectively exhibit cold, warm, and neutral properties; bitter, sweet, and pungent tastes; and tropism to the liver, lung, and stomach meridians, reflecting a therapeutic strategy that clears heat, resolves dampness, and promotes blood circulation. The core triad <i>Eriobotryae Folium</i> (pipaye, PPY), <i>Mori Cortex</i> (sangbaipi, SBP), and <i>Scutellariae Radix</i> and formulas like Erzhi Pills, Sanhuang Lotion, and Xiaoyao Powder suggest key clinical combinations. Network pharmacology revealed that several biological pathways may play important roles in acne treatment, including pathways in cancer, lipid and atherosclerosis, fluid shear stress and atherosclerosis, and chemical carcinogenesis-receptor activation. These pathways are closely linked to inflammation, sebum metabolism, and oxidative stress-core pathological processes in acne vulgaris. Finally, docking showed quercetin, kaempferol, luteolin, and wogonin had strong affinities with AKT1, TNF, IL-6, and TP53 (energies < -5.0 kcal/mol). These findings provide a pharmacological basis for the clinical efficacy of the identified herbs and offer directions for further experimental validation. Crucially, atomistic molecular dynamics simulations and free energy landscape analysis validated the dynamic and thermodynamic stability of these four lowest-energy complexes, confirming that these flavonoids lock the target proteins into deeply stabilized, inactive conformations. Overall, this study bridges clinical experience with dynamic structural biology, providing a high-resolution molecular rationale for anti-acne therapeutics.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"205"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655468","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":"In silico docking and molecular dynamics simulation analysis of phytochemicals targeting human metapneumovirus fusion protein.","authors":"Amna Syeda, Rafat Ali, Md Amjad Beg","doi":"10.1007/s40203-026-00716-2","DOIUrl":"10.1007/s40203-026-00716-2","url":null,"abstract":"<p><p>Human Metapneumovirus (HMPV) continues to be a major cause of respiratory infections around the world, despite the availability of many treatment options and the existence of effective vaccines against other respiratory viruses such as influenza and parainfluenza virus. Since the virus poses a significant public health threat, yet there are no approved antiviral medications or vaccines against it, an effective therapy is still needed. This work aimed to find natural phytochemical inhibitors for HMPV fusion (F) glycoprotein by using a structure-based in silico drug discovery approach. As the protein has an important role in viral attachment to cells and membrane fusion, the choice of HMPV F glycoprotein as a drug target seemed to be appropriate. Compounds from the Indian Medicinal Plants, Phytochemistry and Therapeutics (IMPPAT) 2.0 database were screened by performing molecular docking analysis of their interactions and binding affinities towards the HMPV F protein. The top-ranking molecules were further analyzed by conducting 300-nanosecond molecular dynamics simulations in order to obtain insights into complex stabilities, flexibilities, and conformations. Several phytochemicals showed promising docking results and contributed to structural stabilization of the target protein, especially its heptad repeat and fusion loops regions responsible for membrane fusion. These findings support their potential as fusion inhibitors and offer a promising foundation for future experimental validation and antiviral drug development.</p><p><strong>Graphical abstract: </strong>Human Metapneumovirus (HMPV) causes serious respiratory illness, yet no vaccines or antivirals exist. Using computer-based screening, we tested natural compounds from the IMPPAT 2.0 database against the virus's fusion (F) protein. Several phytochemicals showed stable binding, especially at key functional regions, suggesting they could block viral entry. These results highlight promising natural candidates for future HMPV drug development.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00716-2.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"206"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655503","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":"In silico DFT study, molecular docking interactions, molecular dynamics and toxicological assessment of selected organochlorine-based pesticides.","authors":"Md Jalal Uddin, Md Sadik Hussain Evan, Wahid Salekin Tulin, Mohammad Siad Khan, Jannatul Nayeem, Sarkar M A Kawsar","doi":"10.1007/s40203-026-00712-6","DOIUrl":"10.1007/s40203-026-00712-6","url":null,"abstract":"<p><p>Organochlorine pesticides (OCPs) initially garnered significant attention because of their high efficacy in pest control. However, these compounds have been banned worldwide because they impair environmental biodiversity and adversely affect human health through in vivo exposure. In this study, we employed density functional theory (DFT) with the B3LYP/6-31G (d, p) basis set to evaluate the physicochemical, thermodynamic, and spectral properties of five well-known OCPs, namely, dichlorodiphenyltrichloroethane (<b>DDT</b>), endrin (<b>END</b>), endrin ketone (<b>EDK</b>), aldrin (<b>ALD</b>), and heptachlor epoxide (<b>HCE</b>), through in silico methods. Additionally, molecular docking and non-bonding interactions were calculated to investigate the binding properties and mode(s) of action against serine/threonine-protein kinase PIM-2 (PDB ID: 2IWI) and human estrogen receptor (PDB ID: 6PYF) proteins. Thermodynamic and molecular orbital evaluations revealed that <b>DDT</b> and <b>HCE</b> were highly stable and had the highest binding affinities against 2IWI and 6PYF, respectively. Molecular dynamics (MD) simulations conducted utilizing YASARA dynamics with the AMBER14 force field revealed that <b>EDK</b> and <b>HCE</b> exhibit greater conformational flexibility and stability. ADMET and PASS analyses were performed to determine the biological and toxicological effects of the OCPs. All the OCPs studied exhibited carcinogenic, neurotoxic, endocrine-disrupting, and hepatotoxic effects and can easily pass through the intestinal barrier and blood‒brain barrier, indicating their adverse effects on animals. These evaluations provide awareness of OCP use and a deeper understanding of its biochemical and toxicological effects on the environment and biological systems.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00712-6.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"201"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655517","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":"Repurposing drugs for treating dengue haemorrhagic fever and associated autoimmune diseases.","authors":"Govinda Rao Dabburu, Anjali Garg, Anchal Vishnoi, Neelja Singhal, Manish Kumar","doi":"10.1007/s40203-026-00699-0","DOIUrl":"10.1007/s40203-026-00699-0","url":null,"abstract":"<p><p>Dengue viruses (DENVs) usually cause a mild febrile illness which might flare up in some patients as dengue haemorrhagic fever (DHF) or dengue shock syndrome. Altered expression of autoimmune markers and development of autoimmune diseases was observed in patients exhibiting prolonged dengue symptoms, suggesting a possible correlation between DENVs and autoimmune diseases. Molecular mimicry of the blood coagulation pathway proteins by DENVs might be a potential factor underlying clinical manifestations of DHF. Inhibition of protein-protein interactions (PPIs) in DENV mimicry proteins and human proteins can potentially treat both DHF and, associated autoimmune diseases. In this study, we have performed a systematic in silico analysis of human proteins interacting with DENV mimicry proteins (HPIDMP) as novel drug targets. Potential inhibitors of the HPIDMP were discerned from the DrugBank database following stringent parameters. The protein-ligand interactions were predicted using molecular docking and evaluated with decoy-based validation, molecular dynamics simulations, and MM-PBSA binding free energy calculations. RAF1 targeting drugs Sorafenib and Regorafenib exhibited the most consistent interaction profile across all computational analyses, followed by the SIRT1-targeting compounds selisistat and resveratrol, which demonstrated moderate but consistent computational support. In contrast, the MYH9-artenimol and HSPE1-phenethyl isothiocyanate systems showed comparatively weaker support. On the basis of our results, we propose Sorafenib and Regorafenib as the most promising candidates for in vitro or clinical studies for treatment of DHF and/or DENV-associated autoimmune diseases, followed by Selisistat and Resveratrol. Thus these DrugBank molecules can be incorporated in clinical studies or in vitro testing for treatment of DHF and/or DENV-associated autoimmune diseases. Also, the methods adopted in this study can guide the repurposing of known drugs to treat other pathogen-associated autoimmune diseases.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00699-0.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"199"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655471","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":"Phytochemical screening, in vitro and in silico evaluation of antioxidant, anti-diabetic, antibacterial activities of rhizome extracts from <i>Rhinacanthus nasutus</i> (L.) Kurz (snake jasmine).","authors":"Minoli Apsara Rupasinghe Sudu Dewage, Visal Chamikara Lorensu Hewage, Gershaun Daniel Naveed George, Wasath Weerasinghe","doi":"10.1007/s40203-026-00708-2","DOIUrl":"10.1007/s40203-026-00708-2","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;i&gt;Rhinacanthus nasutus&lt;/i&gt; (L.) Kurz is an herbal plant with distinctive medicinal properties which have been used in Ayurvedic treatments for several diseases. This study explored the preliminary antioxidant, antidiabetic, and antibacterial activities of &lt;i&gt;R. nasutus&lt;/i&gt; rhizomes using both in vitro and computational docking methods. &lt;i&gt;R. nasutus&lt;/i&gt; rhizomes were sequentially extracted using &lt;i&gt;n&lt;/i&gt;-hexane (HRN), chloroform (CRN), and methanol (MRN). These fractions were analysed for total phenolic and flavonoid content. Antioxidant capacity was measured via phosphomolybdate and DPPH scavenging assays, while antidiabetic activity was assessed through glucose adsorption and yeast cell glucose uptake models. Phytochemical profiles were determined using Gas Chromatography-Mass Spectrometry. To understand molecular interactions, computational docking was performed on identified compounds against key enzymes: human erythrocyte catalase, peroxiredoxin, pancreatic &lt;i&gt;α&lt;/i&gt;-amylase, and lysosomal &lt;i&gt;α&lt;/i&gt;-glucosidase. Furthermore, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles and drug-likeness scores were evaluated to predict therapeutic safety and efficacy. Statistical analyses were performed using &lt;i&gt;t&lt;/i&gt;-test and ANOVA. The results showed that MRN gave the highest extraction yield and was the richest in total phenolic and flavonoid contents, whereas HRN showed the highest total antioxidant capacity in the phosphomolybdate assay. In the DPPH assay, CRN exhibited the strongest radical-scavenging activity, but the combined extract (SRN) did not show synergy; instead, the fractional inhibitory index indicated an antagonistic interaction among the fractions. In the antidiabetic assays, MRN demonstrated the greatest glucose uptake by yeast cells and the highest glucose adsorption capacity, suggesting a stronger preliminary glucose-lowering potential than the other fractions. Antibacterial screening showed only weak activity, with HRN producing a small inhibition zone against &lt;i&gt;S. aureus&lt;/i&gt; and no detectable activity against the Gram-negative strains tested. GC-MS identified various terpenoids, quinones, and furan derivatives. In the computational study, compound 1H exhibited the strongest binding affinity for catalase, &lt;i&gt;α&lt;/i&gt;-amylase, and &lt;i&gt;α&lt;/i&gt;-glucosidase, while 2C performed best against peroxiredoxin 5. However, ADMET analysis highlighted physicochemical limitations and potential toxicities that require caution. These preliminary findings indicate that &lt;i&gt;R. nasutus&lt;/i&gt; possesses a significant abundance of bioactive compounds with antioxidant, antidiabetic and antibacterial properties which suggest a basis for future investigation to validate and elucidate molecular mechanisms necessary for their development as therapeutic agents.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Graphical abstract: &lt;/strong&gt;An integrated in vitro and in silico evaluation of the multi-targeted therapeutic potential of &lt;i&gt;Rhinacanthus nasutus&lt;/i&gt; (L.) Kurz","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"203"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655430","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 natural phytochemicals as potential inhibitors of UBE2J1 causing ovarian cancer.","authors":"Zujaja Rehman, Ejaz Rasul, Wisha Asif, Rabail Afzal, Nouman Ali, Nimra Hanif, Muhammad Salik Kamran","doi":"10.1007/s40203-026-00715-3","DOIUrl":"10.1007/s40203-026-00715-3","url":null,"abstract":"<p><p>Ovarian cancer remains one of the most lethal gynecological malignancies due to late diagnosis, limited treatment options, and high recurrence rates. Recent evidence highlights the ubiquitin-proteasome system as a key contributor to cancer progression, with ubiquitin-conjugating enzyme E2 J1 (UBE2J1) emerging as a potential oncogenic target. In this study, a comprehensive in silico drug discovery approach was applied to identify natural phytochemicals capable of inhibiting UBE2J1. Sequence and structural modeling confirmed the reliability of the predicted protein conformation, while protein-protein interaction analysis underscored its central role in ubiquitination pathways. Five plant-derived compounds were screened through molecular docking, among which Withaferin A exhibited the strongest binding affinity (- 8.4 kcal/mol), forming stable hydrogen bonds and hydrophobic interactions with key active site residues. Molecular dynamics simulations further demonstrated the stability of the protein-ligand complex, with favorable RMSD, RMSF, and radius of gyration profiles. ADMET and drug-likeness evaluations revealed that Withaferin A complies with Lipinski's rule of five, possesses good intestinal absorption, and shows non-carcinogenic and non-mutagenic properties. Binding free energy calculations using MM/GBSA supported its strong affinity toward UBE2J1. These findings highlight Withaferin A as a promising natural inhibitor of UBE2J1 and provide a foundation for future experimental validation aimed at developing targeted therapies against ovarian cancer.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"204"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655253","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 drug repurposing identifies flavoxate as a novel NLRP3 inflammasome inhibitor for Alzheimer's disease therapy.","authors":"Gajendra Choudhary, Harshita Rajput, Rutweek Kulkarni, Hadiya Siddiqui, Ajay Prakash, Bikash Medhi","doi":"10.1007/s40203-026-00696-3","DOIUrl":"10.1007/s40203-026-00696-3","url":null,"abstract":"<p><p>Alzheimer's disease (AD) remains a debilitating neurodegenerative disorder with limited therapeutic options, necessitating novel approaches to target its underlying mechanisms. The NLRP3 inflammasome has emerged as a critical player in AD pathogenesis, driving neuroinflammation and amyloid-beta aggregation, yet existing inhibitors face challenges such as hepatotoxicity and poor blood-brain barrier (BBB) penetration. We conducted a computational drug repurposing study to identify FDA-approved drugs with NLRP3 inhibitory potential and favourable BBB permeability. Using molecular docking we screened a library of 2600 FDA approved compounds against the NLRP3 structure (PDB ID:8WSM), followed by molecular dynamics (MD) simulations and binding free energy calculations to validate top hits. Our results identified Flavoxates as the most promising candidate, exhibiting a high docking score (- 10.241 kcal/mol) and stable binding affinity (- 52 kcal/mol via MMPGBSA). MD simulations confirmed its robust interaction with NLRP3, demonstrating low RMSD (0.168 +/- 0.019 nm) and RMSF (0.088 +/- 0.035 nm) values over 100 ns. Moreover, Flavoxate showed optimal pharmacokinetic properties, including BBB permeability and low toxicity, as predicted by SwissADME and ProTox 3.0 The study highlights the efficacy of in silico methods in accelerating drug repurposing, bypassing the need fo de novo drug development. By repurposing Flavoxate, we propose a clinically translatable strategy to mitigate NLRP3-mediated neuroinflammation in AD, offering a potential disease modifying therapy with an established safety profile. This work underscores the significance of computational approaches in bridging the gap between preclinical discovery and therapeutic application for neurodegenerative diseases.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00696-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"200"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655272","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":"<i>α</i> _1A-Adrenergic receptor (<i>ADRA1A</i>) signaling signatures as prognostic biomarkers in liver hepatocellular carcinoma: a bioinformatic analysis.","authors":"Yarely Mabell Beltrán-Navarro, José Vázquez-Prado, Guadalupe Reyes-Cruz, Jesús Adolfo García-Sáinz","doi":"10.1007/s40203-026-00706-4","DOIUrl":"10.1007/s40203-026-00706-4","url":null,"abstract":"<p><p>The <i>α</i> _1A-adrenergic receptor, encoded by <i>ADRA1A</i>, couples to heterotrimeric G_q/11 proteins, promoting intracellular calcium mobilization and PKC activation. In human hepatocytes, it regulates acute metabolic responses and impacts gene expression. Although fundamental hepatic functions of <i>ADRA1A</i> have been described, its role in hepatocellular carcinoma remains elusive. We hypothesized that <i>ADRA1A</i> expressed in liver cancer tissue is part of a signaling repertoire potentially linked to patient outcomes. We analyzed The Cancer Genome Atlas liver cancer datasets and found <i>ADRA1A</i> gene deletion in 6% of patients and more prolonged survival of patients with high <i>ADRA1A</i> expression. Thus, we aimed to identify <i>ADRA1A</i>-signaling partners equally linked to more prolonged patient survival. Through a rational data mining strategy, based on the identification of the signaling repertoire linked to <i>ADRA1A</i> expression and statistical correlation with patient survival, we identified a transcriptional signature integrated by the adrenoceptor and five candidate signaling companions including two RhoGEFs: <i>FGD4</i> and <i>FARP2</i>, a phospholipid phosphatase: <i>PLPP6</i>, a RabGAP: <i>TBC1D2B</i>, and an RTK adaptor: <i>BAIAP2</i>. Additionally, highly co-expressed GPCRs such as <i>ACKR2</i>, <i>DRD1</i>, <i>ADRA1B</i>, <i>GPR17</i>, <i>S1PR1</i>, and <i>GPR182</i>, and RTKs like <i>KDR</i> and <i>TEK</i> similarly integrated transcriptional signatures with <i>ADRA1A</i> that correlated with more prolonged survival. Most <i>ADRA1A</i> candidate signaling partners were well-co-expressed with hepatocyte markers, suggesting that integrating <i>ADRA1A</i>-associated signaling networks could improve liver cancer patients' prognosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00706-4.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"202"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148655220","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":"Integrated network pharmacology and molecular docking based insights into transient receptor potential melastatin3 regulatory mechanism in COPD.","authors":"Shalini Sharma, Subhashini","doi":"10.1007/s40203-026-00707-3","DOIUrl":"https://doi.org/10.1007/s40203-026-00707-3","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a multifactorial airway disorder characterized by chronic inflammation, epithelial dysfunction, and dysregulated intracellular signaling. Transient receptor potential melastatin 3 (TRPM3), a Ca²⁺ permeable ion channel has emerged as a potential regulator of inflammatory and survival pathways, however, its therapeutic relevance in COPD remains poorly understood. The present study integrates network pharmacology and molecular docking to identify putative targets of TRPM3 agonists CIM0216, pregnenolone sulfate (preg sulfate), and nifedipine in COPD. A total of 2442 unique COPD associated genes were identified and integrated with predicted TRPM3 agonist targets revealing 20, 28, and 38 common targets for CIM0216, preg sulfate, and nifedipine, respectively. Enrichment analyses highlighted EGFR tyrosine kinase inhibitor resistance and PI3K/AKT signaling as key COPD related pathways which also correlated with major TFs. Further, AKT1, JAK2, and PTGS2 were identified as central hub genes, particularly associated with CIM0216 and nifedipine. No common hub genes were identified among all three TRPM3 agonists, nor between the CIM0216-preg sulfate and nifedipine-preg sulfate combinations. The hub genes were validated through GEO dataset (GSE57148). The identified miRNAs form a dense regulatory network controlling inflammatory, proliferative, and immune signaling pathways through key transcription factors, underscoring the importance of miRNA-mediated regulation in COPD progression. Molecular docking revealed that CIM0216 exhibited strong binding affinity towards TRPM3 (ΔG =  - 8.6 kcal/mol with 3 hydrogen bonds), AKT1 (ΔG =  - 10.8 kcal/mol with 4 hydrogen bonds), JAK2 (ΔG =  - 9.0 kcal/mol with 4 hydrogen bonds), and PTGS2 (ΔG =  - 9.7 kcal/mol with 6 hydrogen bonds) as compared with nifedipine which showed moderate affinity towards TRPM3 (ΔG =  - 7.1 kcal/mol and 6 hydrogen bonds), AKT1 (ΔG =  - 7.3 kcal/mol and 3 hydrogen bonds), JAK2 (ΔG =  - 6.4 kcal/mol and 2 hydrogen bonds), and PTGS2 (ΔG =  - 7.6 kcal/mol and 11 hydrogen bonds), supporting its potential for effective modulation of COPD associated signaling pathways. The study predicts that CIM0216 might act as a potential multi-target agonist of key inflammatory and survival pathways implicated in COPD. The findings propose a mechanistic insight into TRPM3-mediated signaling and support further experimental validation of TRPM3 agonists as novel therapeutic candidates for COPD.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-026-00707-3.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"208"},"PeriodicalIF":0.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680693","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":"In silico identification of novel PTP1B inhibitors by the investigation of molecular mechanism, QSAR, and DFT studies.","authors":"Humaira Zulfiqar, Samira Akter, Jarin Tasnim, Muhammad Younis, Md Mehedi Hasan, Sidra Manzoor, Sarnop Sarker, Muhammad Waqas, Khan Rajib Hossain","doi":"10.1007/s40203-026-00649-w","DOIUrl":"10.1007/s40203-026-00649-w","url":null,"abstract":"<p><p>Protein tyrosine phosphatase 1B (PTP1B) is a well-known and promising drug target involved in the negative regulation of insulin and leptin signaling, and new anti-diabetic molecules for the treatment of type 2 diabetes are directly in its hands. A series of PTP1B inhibitors was discovered and characterized using in silico techniques, including virtual screening, molecular docking, ADMET profiling, toxicity prediction, VEGA-QSAR analysis, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. A starting library of 1000 anti-diabetic compounds was screened, and PubChem CID 44560696 was identified as the most successful hit. The most potent inhibitor was then identified as CID 44560744 through chemical analogy-based refinement, with a binding free energy of - 9.13 kcal/mol and the ability to form several stabilizing hydrogen bonds and hydrophobic interactions with the key catalytic residues. DFT-optimized geometry and docking revealed that the lead compound shows high stability and strong PTP1B inhibition, showing superior binding affinity compared to ursolic acid, which exhibited a lower binding energy of - 6.34 kcal mol^-1. The MD simulations showed that the PTP1B-ligand complex was structurally stable and compacted during the 200 ns simulation, with desirable profiles for RMSD, RMSF, Rg, SASA, and hydrogen bonds. The DFT and FMO analyses indicated that the compound exhibits extreme chemical reactivity and electron-transfer capability, owing to its low HOMO-LUMO gap, high softness, and moderate electrophilicity. The results of ADMET and toxicity evaluations (SwissADME, ProTox-II, and VEGA-QSAR) pointed to satisfactory solubility, non-carcinogenicity, no mutagenicity, and high pharmacological safety. Overall, the synergy of the computational methods has made CID 44560744 a lead scaffold for the development and optimization of selective PTP1B inhibitors for T2DM therapy.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"14 2","pages":"196"},"PeriodicalIF":0.0,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581941","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}