Current pharmaceutical design最新文献

{"title":"Nutritional Adjuvants in Diabetes: Biotin and Chromium Picolinate as Emerging Therapeutic Agents.","authors":"Manik Mehta, Akanksha Saini, Dinesh Kumar Mehta, Rina Das","doi":"10.2174/0113816128456434260713163014","DOIUrl":"https://doi.org/10.2174/0113816128456434260713163014","url":null,"abstract":"<p><strong>Introduction: </strong>Insulin resistance and type 2 diabetes mellitus (T2DM) are serious worldwide health issues linked to dyslipidaemia, oxidative stress, impaired glucose metabolism, and persistent inflammation. Although their clinical significance is still unknown, micronutrients like chromium and biotin are thought to affect insulin signalling, glucose homeostasis, and lipid metabolism. The purpose of this review is to compile the preclinical, clinical, and epidemiological data that is currently available regarding the individual and combined effects of chromium and biotin on metabolic outcomes, insulin sensitivity, and glycaemic control.</p><p><strong>Methods: </strong>Using databases like PubMed, Scopus, and Google Scholar, a thorough search of narrative literature was carried out. Included were pertinent experimental, clinical, and review studies evaluating the use of chromium and/or biotin supplements in diseases like metabolic syndrome, insulin resistance, and type 2 diabetes. With a focus on study design, dosage, duration, mechanistic pathways, and reported metabolic outcomes, the evidence was qualitatively examined.</p><p><strong>Results: </strong>Preclinical research repeatedly shows that biotin and chromium improve oxidative stress markers, lipid profiles, insulin sensitivity, and glucose tolerance. Increased GLUT-4 translocation, AMPK activation, insulin signalling pathway modulation (IRS-1/PI3K/Akt), and biotin-dependent enzyme regulation are some of the mechanisms that mediate these effects. Particularly in those with poor glycaemic control or micronutrient deficiencies, clinical trials show modest but significant improvements in fasting blood glucose, HbA1c levels, insulin resistance indices, and lipid parameters. Glycaemic control, dyslipidaemia, oxidative stress, and cardiovascular risk markers all seem to improve with combined supplementation. Additionally, epidemiological data point to a negative correlation between dietary chromium consumption and the risk of T2DM.</p><p><strong>Discussion: </strong>The results demonstrate the complementary functions of biotin and chromium in controlling the metabolism of fats and carbohydrates. When taken together, they may provide greater metabolic advantages than when taken separately. However, the generalisability of findings is constrained by variations in study design, participant characteristics, supplement formulations, and baseline nutritional status. The necessity of standardized research methods is highlighted by these discrepancies.</p><p><strong>Conclusion: </strong>In general, chromium and biotin exhibit promise as supplemental treatments for the treatment of insulin resistance and type 2 diabetes, especially in populations with nutritional deficiencies or metabolic disorders. However, more extensive, carefully planned randomized controlled trials are needed to ascertain the best dosage, long-term safety, and clinical effectiveness.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Network Pharmacology and Experimental Study: Bioactive Compounds and Mechanisms of XuanTong BuLuo Decoction in Treating Diabetic Cardiomyopathy.","authors":"Min Wang, Kaijie Xie, Hao Liu, Xiaoxi Zhang, Weixue Wang","doi":"10.2174/0113816128442804260608055805","DOIUrl":"https://doi.org/10.2174/0113816128442804260608055805","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetic Cardiomyopathy (DCM) is a serious diabetic complication with limited therapies. While XuanTong BuLuo Decoction (XTBLD) benefits diabetic complications, its active components and anti-DCM mechanisms are unclear. This study aimed to predict XTBLD's active ingredients, key targets, and related pathways against DCM via network pharmacology, and verify them by animal experiments.</p><p><strong>Methods: </strong>Network pharmacology and molecular docking were used to screen XTBLD's active components, potential targets against DCM, and their binding affinity. Animal experiments evaluated XTBLD's therapeutic effects on DCM by assessing glycemic control, inflammation, and key protein expression in related pathways.</p><p><strong>Results: </strong>A total of 173 active ingredients were screened from XTBLD, with 217 intersecting genes obtained. Enrichment analysis revealed 125 signaling pathways, with 11 involved in XTBLD against DCM. Five main active components were identified using UPLC-MS/MS. In diabetic mice, XTBLD showed positive effects on blood glucose control, inflammatory response, and creatine kinase isoenzyme levels, as well as the expression of cyclin-dependent kinase inhibitor 1 and insulin-like growth factor binding protein 3.</p><p><strong>Discussion: </strong>This study demonstrates that XTBLD exerts cardioprotective effects against DCM via regulating its key active components, core targets (CDKN1A, IGFBP3), and related signaling pathways, providing a scientific basis for XTBLD's clinical application in DCM management.</p><p><strong>Conclusion: </strong>XTBLD may exhibits a potential protective effect on glycemic control and myocardial injury by regulating signaling pathways associated with cell growth, apoptosis, and inflammatory responses, with puerarin, luteolin, formononetin, kaempferol, and quercetin proposed as its potential main active components.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Candida albicans Infections through Synergistic Phytochemical and Antifungal Combinations.","authors":"Arya Sharma, Harshita Singhai, Sunny Rathee, Sakshi Soni, Umesh K Patil","doi":"10.2174/0113816128499052260715140756","DOIUrl":"https://doi.org/10.2174/0113816128499052260715140756","url":null,"abstract":"<p><p>Candida albicans remains a major clinical threat because of its highly invasive nature, affecting mucosal surfaces and superficial tissues and possessing the ability to progress to life-threatening systemic infections, particularly in immunocompromised individuals. The extensive use of conventional antifungal agents has contributed to the emergence of antifungal resistance and dose-limiting toxicity, highlighting the need for alternative therapeutic strategies. Recent studies have demonstrated that combining plant-derived phytoconstituents with conventional antifungal drugs enhances therapeutic efficacy against C. albicans while reducing the development of antifungal resistance. This review explores the synergistic interactions between phytochemicals and standard antifungal agents, emphasizing their mechanistic roles in potentiating the activity of azoles, polyenes, and echinocandins through multi-targeted mechanisms. These mechanisms include disruption of fungal cell membrane integrity, inhibition of drug efflux pumps, induction of mitochondrial dysfunction, and generation of oxidative stress. Collectively, these effects impair fungal virulence, inhibit biofilm formation, enhance antifungal susceptibility, and improve treatment outcomes. Furthermore, such combinatorial approaches permit dose reduction of conventional antifungal agents, thereby minimizing drug-associated toxicity and slowing the emergence and progression of antifungal resistance.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148600053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Natural Bioactive Compounds for Ocular Health: A Comprehensive Review.","authors":"Hemant Ahirwar, Harshita Singhai, Sunny Rathee, Sakshi Soni, Umesh K Patil","doi":"10.2174/0113816128473797260709112308","DOIUrl":"https://doi.org/10.2174/0113816128473797260709112308","url":null,"abstract":"<p><p>Ocular disorders such as age-related macular degeneration, cataract, dry eye disease, and diabetic retinopathy represent a growing global public health burden. Natural bioactive compounds, particularly carotenoids, flavonoids, and traditional herbal extracts, have demonstrated significant antioxidant, antiinflammatory, and neuroprotective effects on ocular tissues. However, the clinical translation of these phytomolecules is often limited by poor solubility, low stability, and inadequate ocular bioavailability. Recent advances in nanotechnology have enabled the development of targeted delivery platforms, including nanoparticles, nanoemulsions, hydrogels, and liposomes, which enhance tissue-specific delivery, bioavailability, and therapeutic efficacy. This review critically evaluates current evidence from in vitro, in vivo, and clinical studies on the role of natural compounds in ocular health, highlighting their mechanisms of action, safety profiles, and pharmacological potential. Furthermore, the integration of traditional medicinal systems with modern ophthalmic strategies, supported by personalised nanoformulation approaches, offers promising avenues for holistic and patient-centred eye care. Key challenges related to standardisation, regulatory compliance, quality control, and large-scale manufacturing are discussed, along with future directions for bioprospecting novel ocular bioactives and advancing integrative strategies for sustainable eye health management.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review of Phosphodiesterases 4 (PDE4) Inhibitors in Clinical Trials.","authors":"Raghu Prasad Mailavaram, Yogesh Chaudhari, Ritesh S Tarwani, Katharigatta N Venugopala, Manik Ghosh, Prasenjit Maity, Pran Kishore Deb","doi":"10.2174/0113816128436242260714073027","DOIUrl":"https://doi.org/10.2174/0113816128436242260714073027","url":null,"abstract":"<p><p>Phosphodiesterase 4 (PDE4) facilitates the enzymatic breakdown of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), through its four distinct isotypes, namely PDE4A to PDE4D, along with more than 25 splice variants. It plays a crucial role in cancer development, respiratory issues such as asthma and chronic obstructive pulmonary disease (COPD), autoimmune diseases like psoriasis, and neurological disorders such as Alzheimer's disease. Various methods are being developed to enhance clinical efficacy and reduce side effects. Some of these methods include drug delivery via inhalation and the development of non-emetic PDE4 inhibitors and mixed PDE inhibitors. These inhibitors offer several advantages over traditional formulations, including selectivity for specific inhibitors, targeted tissue distribution, and oral effectiveness. All these efforts have led to the emergence of novel PDE4 inhibitors, with some having progressed to clinical trial stages and others approved as medications. This review summarises PDE4 inhibitors currently in clinical trials, highlighting their therapeutic potential, limitations, and future prospects.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing Lipid-Based Nanocarriers for Skin Cancer Therapy: A Comprehensive Review of Drug Delivery, Gene-Based Strategies, and Clinical Translation.","authors":"Viresh Kumar, Nisha Bharti, Manish Kumar","doi":"10.2174/0113816128463662260612132215","DOIUrl":"https://doi.org/10.2174/0113816128463662260612132215","url":null,"abstract":"<p><p>Skin cancer, including melanoma and non-melanoma subtypes, remains a major global health challenge with steadily rising incidence rates. Although conventional treatment modalities such as surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy have improved patient outcomes, their clinical effectiveness is frequently limited by poor cutaneous penetration, systemic toxicity, non-specific drug distribution, and the emergence of drug resistance. In this context, lipid-based nanocarriers (LBNCs) have emerged as a promising strategy to address these therapeutic limitations. This comprehensive review highlights recent advances in LBNCs, including liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), transferosomes, ethosomes, and invasomes, for the management of skin cancer. The review discusses the physicochemical properties and mechanisms by which these nanocarriers enhance topical and transdermal drug delivery by overcoming the stratum corneum barrier through hydration, lipid fluidization, and follicular targeting. Furthermore, the role of LBNCs in achieving tumor-specific accumulation via passive targeting through the enhanced permeability and retention (EPR) effect, as well as active targeting using ligandfunctionalized systems, is critically examined. Particular emphasis is placed on lipid nanoparticles as nonviral vectors for gene therapy, enabling the efficient delivery of nucleic acids such as siRNA, mRNA, and CRISPR/Cas9 components to modulate oncogenic pathways. Recent preclinical and clinical developments, including personalized mRNA-based cancer vaccines, are summarized to demonstrate the translational potential of LBNCs. Overall, this review underscores the versatility of lipid-based nanocarriers as multifunctional, biocompatible, and patient-friendly platforms, offering new opportunities for precise, effective, and personalized skin cancer therapy.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and In vivo Based Multi-Target Therapy and Prognostic Bio-modeling in Liver Cancer.","authors":"Madiha Jabeen Abbasi, Rashid Abbasi, Ding Xianfeng","doi":"10.2174/0113816128421211260214133902","DOIUrl":"https://doi.org/10.2174/0113816128421211260214133902","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular Carcinoma, being 3rd most aggressive malignancy with complex multifactorial etiologies become a major public health issue worldwide. The critical and unknown molecular environment raised multiple challenges for oncologists, which is resulting in poor earlier detection with unsatisfactory treatment options in patients.</p><p><strong>Methods: </strong>This study determined the cancer regulatory networks and interaction mechanism of five distinctive genes (CTNNB1TTN, TERT, ALB, OBSCN) in HCC by using comprehensive statistical-based machine learning and system biology approaches. This work implemented redundancy analysis of genes by CRISPRCas9 and RNAi technique, accompanied by identification of transcription factors, kinases, and intermediate proteins associated with key genes. Network Pharmacology with molecular docking and dynamics simulation followed by in-vitro verification is used to evaluate anti-cancer drug activity against TERT.</p><p><strong>Results: </strong>The results declared a high frequency of genetic alteration in genes at the allelic level with enrichment in several oncogenic signaling pathways, including stem cell proliferation and transferase activity, etc. Among key genes, TERT is being analyzed for drug discovery in HCC. The molecular docking studies of TERT with ambrisentan revealed high binding energy, which was further investigated by molecular dynamics studies and ADMET evaluation. An in vitro wet lab experiment (MTT assay) is designed to determine the cytotoxicity of the drug in the HepG2 cell line.</p><p><strong>Discussion: </strong>Current research has discovered the most effective pharmacological targets through a full understanding of their genetic mechanisms. Biomarker-based treatments provide a more precise diagnostic assessment of HCC genetics and progression.</p><p><strong>Conclusion: </strong>The findings of this study enlightened identified targets as the scientific foundation for HCC therapeutics using integrated network analysis and molecular dynamics simulations.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148519960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Mechanism of Shenqi Fuzheng Injection on Alleviating EGFR-TKIs Resistance in Non-small Cell Lung Cancer: Integration of Clinical Observation, Network Pharmacology, and Experimental Validation.","authors":"Jiali Wang, Can Li, Xianhai He, Zhirong Jia, Changjiang Liu, Junqing Yang, Mingyu Fang, Jieru Zhou, Xiaohan Peng, Xiaoying Liu, Yongsheng Wang, Xuansheng Ding","doi":"10.2174/0113816128474105260604054207","DOIUrl":"https://doi.org/10.2174/0113816128474105260604054207","url":null,"abstract":"<p><strong>Introduction: </strong>Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors (EGFR-TKIs) are the first-line therapy for EGFR-mutant Non-Small Cell Lung Cancer (NSCLC), but drug resistance limits their long-term efficacy. This study aimed to identify prognostic biomarkers for NSCLC patients receiving EGFRTKIs monotherapy or EGFR-TKIs combined with Shenqi Fuzheng Injection (SFI), and to elucidate the role of SFI in alleviating resistance.</p><p><strong>Methods: </strong>A cohort of 208 patients with advanced NSCLC receiving EGFR-TKIs therapy was enrolled to construct a prognostic model, and a retrospective analysis of 104 patients compared EGFR-TKIs monotherapy with the SFI combination was conducted. Network pharmacology analysis identified active ingredients, targets, and pathways of SFI. Finally, these findings were validated through in vitro experiments, and the potential mechanism was explored.</p><p><strong>Results: </strong>A prognostic model for patients with advanced NSCLC treated with EGFR-TKIs was constructed and validated. The combination of SFI and EGFR-TKIs significantly delayed disease progression by modulating inflammation and lipid metabolism. Network pharmacology revealed the targets (including IL-6 and PPARγ) and pathways that SFI modulates. Molecular docking revealed stable binding between the core components of SFI and PPARγ. In vitro experiments confirmed that SFI attenuated resistance by inhibiting the IL-6/PPARγ axis.</p><p><strong>Discussion: </strong>This study identifies the IL-6/PPARγ axis as the key target of SFI, alleviating resistance, providing a mechanistic basis for SFI as an adjuvant to EGFR-TKIs in NSCLC.</p><p><strong>Conclusion: </strong>These findings establish a clear link between clinical observation and molecular mechanism. SFI improves the efficacy of EGFR-TKIs by modulating inflammation and lipid metabolism, primarily through suppressing the IL-6/PPARγ axis.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Neurohormonal Modulators in Reducing Adverse Outcomes in Patients with Ischemic Heart Disease.","authors":"Arjun Talukdar, Prasanti Sharma, Sayak Khawas, Neelima Sharma","doi":"10.2174/0113816128450453260624145317","DOIUrl":"https://doi.org/10.2174/0113816128450453260624145317","url":null,"abstract":"<p><p>Neurohormonal modulators mitigate adverse outcomes in ischemic heart disease (IHD) by targeting maladaptive activation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS), both of which contribute to disease progression. This narrative review summarizes and critically evaluates conventional and emerging neurohormonal modulators in IHD management. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and angiotensin receptor-neprilysin inhibitors (ARNIs) counteract vasoconstriction, inflammation, fibrosis, and adverse ventricular remodelling. ACE inhibitors and ARBs reduce RAAS-mediated injury, while beta-blockers limit myocardial oxygen demand and arrhythmia risk by attenuating SNS overactivation. MRAs block aldosterone-mediated sodium retention and myocardial fibrosis, whereas ARNIs enhance natriuretic peptide signaling to mitigate fluid overload and structural remodeling. In addition, sodium- glucose cotransporter-2 (SGLT2) inhibitors improve metabolic efficiency and hemodynamic stability, extending the benefits of neurohormonal modulation beyond traditional pathways. Collectively, these agents improve cardiac function, reduce hospitalizations, and enhance survival, as demonstrated in clinical trials. This review highlights their complementary mechanisms, current limitations, and future therapeutic directions, underscoring their central role in contemporary IHD management and in improving quality of life.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Insights into 1,4-Naphthoquinones as Allosteric MEK1 Inhibitors for Cancer Therapy.","authors":"Mohd Rehan","doi":"10.2174/0113816128449207260701111652","DOIUrl":"https://doi.org/10.2174/0113816128449207260701111652","url":null,"abstract":"<p><strong>Introduction: </strong>MEK1 plays a critical role in cellular survival and proliferation. Its activity is tightly regulated, and its dysregulation may lead to various cancers. It is frequently targeted for therapeutic intervention. 1,4-Naphthoquinones, a natural compound class, have garnered increasing interest for their anticancer potential.</p><p><strong>Methods: </strong>A comprehensive library of 1,4-naphthoquinones was obtained from the PubChem database. This library was subjected to virtual screening using molecular docking against the allosteric site of MEK1 kinase. Selection was based on DOCK scores and pose similarity to the native inhibitor BBM. Ten compounds were selected and analyzed in detail for binding affinity, binding poses, and molecular interactions. Molecular dynamics (MD) simulation was performed for the top candidate.</p><p><strong>Results: </strong>The ten shortlisted compounds exhibited strong binding affinities for MEK1. Key residues involved in binding, including Asp-190, Asp-208, Phe-209, Met-219, and Lys-97, were consistently engaged by the shortlisted compounds and the native inhibitor. MD simulation of the top compound confirmed its stable binding. Pose overlay revealed that similar scaffolds showed comparable binding energies and interactions. ADMET predictions were considered in hit prioritization.</p><p><strong>Discussion: </strong>Early enrichment of true positives over decoys strongly supports the screening protocol. The common key residues shared between the naphthoquinones and the native inhibitor suggest a similar inhibitory mechanism. ADMET-based predictions led to the identification of the five most promising candidates.</p><p><strong>Conclusion: </strong>This study proposed ten 1,4-naphthoquinones as potential allosteric inhibitors of MEK1. After integrating DOCK scores, binding energy, and ADMET risk, five compounds emerged as the most promising. These results provide a computational foundation for further testing.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}