Omics A Journal of Integrative Biology最新文献

{"title":"Effect of Genetic Ancestry on Phenotypes and Genotypes in Papillary Thyroid Cancer.","authors":"Shun-Yu Chi, Yi-Chiung Hsu, Shih-Ping Cheng","doi":"10.1089/omi.2024.0189","DOIUrl":"10.1089/omi.2024.0189","url":null,"abstract":"<p><p>Thyroid cancer (THCA) is a prevalent health burden, and unpacking its biological and social determinants is a public health priority. Previous studies have reported inconsistent findings regarding the effects of race and ethnicity on the incidence and presentation of THCA. It remains unclear whether racial differences manifest at the molecular level. By harnessing the Cancer Genome Atlas papillary THCA dataset, this study derived genetic ancestry estimates from single nucleotide polymorphism array genotyping and exome sequencing data. Five ancestral groups (Europeans, East Asians, Africans, Native/Latin Americans, and South Asians) were included for analysis. We found a good agreement between genetic ancestry and reported race (Cramer's V = 0.730). Although differences in tumor size and patient age were observed, overall survival, progression-free interval, and disease-free interval were similar across the ancestral groups. Furthermore, the distribution of oncogenic drivers did not significantly differ among these groups. Weighted gene co-expression network analysis identified several ancestry-associated signatures. In conclusion, this study suggests that hereditary ancestral traits likely have little biological significance in papillary THCA. Instead, racial disparities in this type of cancer may be attributed to lifestyle factors, environmental exposures, and social and political power asymmetries in society and healthcare infrastructure.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"117-124"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theranostic Target NSUN2, a C(5)-Methyltransferase, Phospho-Regulatory Network Uncovered with Systematic Assembly of 805 Datasets.","authors":"Fathimathul Lubaba, Mejo George, Mukhtar Ahmed, Levin John, Athira Perunelly Goplakrishnan, Prathik Basthikoppa Shivamurthy, Susmi Varghese, Priyanka Pahal, Mahammad Nisar, Poornima Ramesh, Inamul Hasan Madar, Rajesh Raju","doi":"10.1089/omi.2025.0025","DOIUrl":"10.1089/omi.2025.0025","url":null,"abstract":"<p><p>The RNA cytosine C(5)-methyltransferase NSUN2 is involved in RNA modification and regulates gene expression and genomic stability. Beyond multiple sequence/copy number variations, NSUN2 displays altered phosphoprotein expression in various cancers and developmental disorders, thereby making it a prime molecular target of relevance to both therapeutics and diagnostics, that is, theranostics. Despite its key role in kinase-regulated pathways and broader biological processes, the phospho-regulatory network of NSUN2 remains largely unexplored. We report here a systematic assembly of 805 phosphoproteomics datasets from the literature, among which 239 datasets showed differential regulation of NSUN2 phosphopeptides and 40 ensembled phosphosites in NSUN2. Significantly, the phosphorylation sites Ser456, Ser743, and Ser751 represented NSUN2 in ∼50% of these datasets. This is notable given that the functional roles of these phosphosites have been previously underappreciated and underrepresented in the scientific literature. Therefore, we implemented a codetection/coregulation approach based on the phosphosites in other proteins that are codifferentially regulated with phosphopeptides of NSUN2. This approach led to our identification of 55 interactors, 4 potential kinases, and 7 other methylases whose phosphopeptides were codifferentially regulated with NSUN2 phosphopeptides. To the best of our knowledge, this study provides the first phosphosite-centric regulatory network model of NSUN2 to employ theranostic strategies for targeting NSUN2 in cancers and other disorders.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"164-177"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Scale Metabolic Modeling of Human Pancreas with Focus on Type 2 Diabetes.","authors":"Mustafa Sertbas, Kutlu O Ulgen","doi":"10.1089/omi.2024.0211","DOIUrl":"10.1089/omi.2024.0211","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is characterized by relative insulin deficiency due to pancreatic beta cell dysfunction and insulin resistance in different tissues. Not only beta cells but also other islet cells (alpha, delta, and pancreatic polypeptide [PP]) are critical for maintaining glucose homeostasis in the body. In this overarching context and given that a deeper understanding of T2D pathophysiology and novel molecular targets is much needed, studies that integrate experimental and computational biology approaches offer veritable prospects for innovation. In this study, we report on single-cell RNA sequencing data integration with a generic Human1 model to generate context-specific genome-scale metabolic models for alpha, beta, delta, and PP cells for nondiabetic and T2D states and, importantly, at single-cell resolution. Moreover, flux balance analysis was performed for the investigation of metabolic activities in nondiabetic and T2D pancreatic cells. By altering glucose and oxygen uptakes to the metabolic networks, we documented the ways in which hypoglycemia, hyperglycemia, and hypoxia led to changes in metabolic activities in various cellular subsystems. Reporter metabolite analysis revealed significant transcriptional changes around several metabolites involved in sphingolipid and keratan sulfate metabolism in alpha cells, fatty acid metabolism in beta cells, and myoinositol phosphate metabolism in delta cells. Taken together, by leveraging genome-scale metabolic modeling, this research bridges the gap between metabolic theory and clinical practice, offering a comprehensive framework to advance our understanding of pancreatic metabolism in T2D, and contributes new knowledge toward the development of targeted precision medicine interventions.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"125-138"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven Hub Genes Associated with Huntington's Disease and Diagnostic and Therapeutic Potentials Identified by Computational Biology.","authors":"Afzal Hussain, Taj Mohammad, Shumayila Khan, Mohamed F Alajmi, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan","doi":"10.1089/omi.2025.0006","DOIUrl":"10.1089/omi.2025.0006","url":null,"abstract":"<p><p>Huntington's disease (HD) is characterized by progressive motor dysfunction and cognitive decline. Early diagnosis and new therapeutic targets are essential for effective interventions. We performed integrative analyses of mRNA profiles from three microarrays and one RNA-seq dataset from the Gene Expression Omnibus database. The datasets included were GSE8762, GSE24250, GSE45516, and GSE64810. Data pre-processing included background correction, normalization, log2 transformation, probe-to-gene symbol mapping, and differential expression analysis. We identified 80 differentially expressed genes (DEGs) based on a significance threshold (<i>p</i> < 0.05) and absolute log fold change (logFC) >0.65. Additionally, we conducted Gene Ontology (GO) and pathway analyses of the identified genes. Protein-protein interactions among DEGs revealed a network from which seven hub genes (<i>VIM, COL1A1, COL3A1, COL1A2, DCN, CXCR2,</i> and <i>S100A9</i>) were identified using the cytoHubba plugin in Cytoscape software. Two top DEGs, <i>IGHG1</i> (up-regulated) and <i>PITX1</i> (up-regulated), also hold potential as therapeutic targets. Insofar as biological contextualization of the findings is concerned, the top enriched GO terms were skeletal system development, blood vessel development, and vasculature development. Molecular function terms highlighted signaling receptor binding, extracellular matrix structural constituent, and platelet-derived growth factor binding. Notably, the significant KEGG pathways included amoebiasis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. In conclusion, the present computational biology integrative analyses of multiple datasets discovered new DEGs and seven hub genes, shedding light on molecular mechanisms of HD. These findings call for translational clinical omics research and may potentially lead to future precision medicine interventions and novel diagnostic biomarkers and therapeutic targets.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"154-163"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic Pulmonary Fibrosis: <i>In Silico</i> Therapeutic Potential of Doxycycline, Pirfenidone, and Nintedanib, and the Role of Next-Generation Phenomics in Drug Discovery.","authors":"Sanjukta Dasgupta","doi":"10.1089/omi.2024.0213","DOIUrl":"10.1089/omi.2024.0213","url":null,"abstract":"<p><p>Innovation in drug discovery for human diseases stands to benefit from systems science and next-generation phenomics approaches. An example is idiopathic pulmonary fibrosis (IPF) that is a chronic pulmonary disorder leading to respiratory failure and for which preventive and therapeutic medicines are sorely needed. Matrix metalloproteinases (MMPs), particularly MMP1 and MMP7, have been associated with IPF pathogenesis and are thus relevant to IPF drug discovery. This study evaluates the comparative therapeutic potentials of doxycycline, pirfenidone, and nintedanib in relation to MMP1 and MMP7 using molecular docking, molecular dynamics simulations, and a next-generation phenomics approach. Adsorption, distribution, metabolism, excretion, and toxicity analysis revealed that doxycycline and nintedanib adhered to Lipinski's rule of five, while pirfenidone exhibited no violations. The toxicity analysis revealed favorable safety profiles, with lethal dose 50 values of doxycycline, pirfenidone, and nintedanib being 2240kg, 580, and 500 mg/kg, respectively. Homology modeling validated the accuracy of the structures of the target proteins, that is, MMP1 and MMP7. The Protein Contacts Atlas tool, a next-generation phenomics platform that broadens the scope of phenomics research, was employed to visualize protein contacts at atomic levels, revealing interaction surfaces in MMP1 and MMP7. Docking studies revealed that nintedanib exhibited superior binding affinities with the candidate proteins (-6.9 kcal/mol for MMP1 and -7.9 kcal/mol for MMP7) compared with doxycycline and pirfenidone. Molecular dynamics simulations further demonstrated the stability of protein-ligand complexes. These findings highlight the notable potential of nintedanib in relation to future IPF therapeutics innovation. By integrating <i>in silico</i> and a next-generation phenomics approach, this study opens up new avenues for drug discovery and development for IPF and possibly, for precision/personalized medicines that consider the molecular signatures of therapeutic candidates for each patient.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"87-95"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Targeting of Interleukin-2-Inducible T-Cell Kinase (ITK) for Cancer and Immunological Disorders: Potential Next-Generation ITK Inhibitors.","authors":"Shazia Ahmed, Mohammad Umar Saeed, Arunabh Choudhury, Taj Mohammad, Afzal Hussain, Mohamed F AlAjmi, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan","doi":"10.1089/omi.2024.0207","DOIUrl":"10.1089/omi.2024.0207","url":null,"abstract":"<p><p>Interleukin-2-inducible T-cell kinase (ITK) is a critical tyrosine kinase enzyme that is involved in the activation and differentiation of T cells. ITK is mainly found in T cells, which plays an essential role in controlling T-cell receptor signaling and downstream pathways. ITK regulates the synthesis of cytokines, particularly interleukin-2 (IL-2), and the development of Th2 cells. ITK is of interest for drug discovery and molecular targeting in immunology, autoimmune diseases, and cancer. Here, we report a structure-based virtual screening utilizing a collection of small molecules obtained from the PubChem database with an eye on the discovery of drugs targeting ITK. The compounds were selected according to compliance with the Lipinski's rule of five. The molecular docking investigation focused on prioritizing binding affinity and specific interaction toward the kinase domain. The highest-ranking search results were subjected to identification of possible pan-assay interference compounds (PAINS), assessment of pharmacokinetic properties, and estimation of pharmacological activity using Prediction of Activity Spectra of Substances (PASS) analysis. The interactions among these chemicals and the salient residues in the interleukin-2-inducible T-cell kinase (ITK) kinase domain were unpacked using a two-dimensional approach. The reference inhibitor ITK-Inhibitor-2 (IMM) and four elucidated compounds with PubChem CIDs, namely, 90442621 (PFB), 141764004 (FTP), 149213796 (FPP), and 145983307 (MBD), showed significant binding affinity of -8, -10.4, -9.8, -10.2, and -10.7 kcal/mol, respectively, and high selectivity for the ITK binding pocket. In conclusion, this study reports on the potential of several compounds for therapeutic targeting of ITK. Furthermore, structural analysis revealed the interaction of proposed compounds and active site residues within the ATP-binding pocket is highly similar to known inhibitors but shares distinct interaction patterns that could improve specificity. This specificity and optimization hold potential for the development of next-generation ITK inhibitors with possible applications in the treatment of immune-related disorders and cancers. Further <i>in vitro</i>, <i>in vivo</i>, and translational clinical research are called for.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"105-115"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabesity: New Candidate Genes and Structural and Functional Effects of Non-Synonymous Single Nucleotide Polymorphisms Identified by Computational Biology.","authors":"Naveenn Kumar, Karthiga Selvaraj, Lakshmiganesh Kadumbur Gopalshami, Riitvek Baddireddi, Kothai Thiruvengadam, Baddireddi Subhadra Lakshmi","doi":"10.1089/omi.2024.0184","DOIUrl":"10.1089/omi.2024.0184","url":null,"abstract":"<p><p>Diabesity is a comorbidity of type 2 diabetes mellitus and obesity. Diabesity is a major global epidemic and a veritable planetary health burden. With diabesity, several clinical signs are present such as excess accumulation of fat, altered lipid metabolism, chronic inflammation, insulin resistance, disordered pancreatic β-cell metabolism, and hyperglycemia. We report here new potential candidate genes for diabesity, and the structural and functional effects of non-synonymous single nucleotide polymorphisms (nsSNPs) in these genes using a computational biology approach. A protein-protein interaction (PPI) network was constructed using Human Integrated Protein-Protein Interaction rEference (HIPPIE') data for 186 diabesity-associated genes from the Disease Gene Network (DisGeNET). Subsequently, the top 2% of nine centrality-ranked genes were identified as hub genes. Gene ontology enrichment analysis was performed with the same gene list using the Gene Ontology enRIchment anaLysis and visuaLizAtion (GORILLA) tool, and importantly, 63 enriched hub genes with no prior disease association were selected and their differential expressions in adipose, skeletal, and hepatic tissues were analyzed using Gene Expression Omnibus (GEO) profiles. Finally, the nsSNPs in the top five prioritized genes (<i>EGFR</i>, <i>SRC</i>, <i>SQSTM1</i>, <i>CCND1</i>, and <i>RELA</i>) were retrieved from Database of Single Nucleotide Polymorphisms (dbSNP) and subjected to deleterious variant analysis. The significant variants were subjected to structural prediction using AlphaFold, stability analysis, and molecular dynamics simulation using GROningen MAchine for Chemical Simulations (GROMACS). Taken together, the present computational biology research reports new molecular insights on diabesity candidate genes and the role of nsSNPs that may potentially contribute to diabesity. As diabesity and diabetes continue to be major planetary health challenges, these findings warrant further <i>in vitro</i> and clinical translation research with an eye to precision medicine and therapeutics innovation. Understanding the differences between wild type and variant proteins is crucial for developing interventions aimed at stabilizing these proteins in the prevention and treatment of diabesity.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"96-104"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in Core-Shell Nanoparticles: Advancing Drug Delivery Solutions and Precision Medicine.","authors":"Suren A Ramadhan, Diyar S Ali","doi":"10.1089/omi.2024.0182","DOIUrl":"10.1089/omi.2024.0182","url":null,"abstract":"<p><p>Drug delivery innovation is an important pillar of systems pharmacology wherein nanotechnology offers significant prospects. This expert review examines and unpacks how core-shell nanoparticles (NPs) could revolutionize drug delivery systems and play a key role in advancing personalized and precision medicine. Core-shell NPs have gained attention as flexible tools for drug delivery due to their distinct structure, which features a core material enclosed by a protective shell. This setup offers multiple benefits, such as effective drug encapsulation, shielding the drug from degradation, and allowing for controlled release. Accordingly, the core serves as a safe storage area for the drug while the shell manages the release speed, providing added stability and supporting sustained delivery. By enabling targeted drug release, this controlled mechanism can help improve treatment outcomes and reduce side effects. Various materials, including polymers, lipids, and inorganic substances create these NPs. Biodegradable polymers, such as poly(lactic-co-glycolic acid) and poly(lactic acid), are popular choices because they offer adjustable degradation rates, which further control how the drug is released. These materials can be tailored for better drug loading, compatibility with the host organism, and specific chemical properties to suit different therapeutic needs. Research into core-shell NPs has been advancing in many therapeutic areas, highlighting their potential for drug delivery innovations. The potential of core-shell NPs to revolutionize drug delivery is not just a possibility but a promising reality that could significantly advance the field of personalized/precision medicine.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"73-86"},"PeriodicalIF":2.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoinformatics: A Veritable Toolbox for Livestock Omics and Veterinomics.","authors":"Ragothaman M Yennamalli, Suneel K Onteru","doi":"10.1089/omi.2024.0208","DOIUrl":"10.1089/omi.2024.0208","url":null,"abstract":"<p><p>Immunoinformatics, an integrative field consisting of bioinformatics and immunology, has showcased its potential in addressing zoonotic diseases, as evidenced during the Coronavirus disease 2019 (COVID-19) pandemic. However, its application in livestock health remains largely untapped. This opinion commentary explores how immunoinformatics, combined with advancements in genomics, multi-omics integration, and genome editing technologies, can revolutionize livestock management by enhancing disease resistance, vaccine development, and productivity. We examine the current and critical challenges, such as limited breed-specific data, computational barriers, and economic constraints, while highlighting the transformative potential of immunoinformatics in addressing these issues. We underscore the importance of leveraging immunoinformatics to bridge the phenotype-genotype gap, develop effective diagnostics and vaccines, and tackle emerging pathogens with zoonotic potential. By emphasizing interdisciplinary collaboration and the need for accessible veterinomics solutions, particularly in low- and middle-income countries, we outline herein the actionable steps to harness immunoinformatics for sustainable livestock management and global food security. In all, this opinion commentary aims to inspire a renewed focus on and veritable innovations in planetary health by unpacking and recognizing immunoinformatics' key role in shaping the future of veterinomics, the convergence of veterinary medicine with omics systems science, in the pursuit of agricultural sustainability.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"32-35"},"PeriodicalIF":2.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals Withanolide N and Dryobalanolide as Potential Bioactive Leads for Developing Anticancer Drugs Targeting Tyrosine-Protein Kinase Mer.","authors":"Afzal Hussain, Taj Mohammad, Mehak Gulzar, Mohamed F Alajmi, Dharmendra Kumar Yadav, Md Imtaiyaz Hassan","doi":"10.1089/omi.2024.0192","DOIUrl":"10.1089/omi.2024.0192","url":null,"abstract":"<p><p>There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment. Hence, tyrosine-protein kinase Mer has emerged as one of the key factors in cancer susceptibility and metastasis and, by extension, as a potential target of relevance for cancer drug resistance. Here, we report, using an integrated virtual screening and simulation of phytochemicals from the IMPPAT 2.0 library, phytochemicals withanolide N and dryobalanolide as potential bioactive leads for developing anticancer drugs targeting tyrosine-protein kinase Mer. The study employed an integrated design, including physicochemical property analyses, binding affinity calculations, pan-assay interference compounds filtering, absorption, distribution, metabolism, excretion, and toxicity, and PASS analyses, <i>in silico</i> molecular dynamics simulations, followed by principal component analysis and free energy landscape. We call for further evaluation, validation, and translational medical research on these two phytochemicals <i>in vitro</i> and <i>in vivo</i>, with an eye to their putative therapeutic efficacy and safety in the field of oncology and anticancer drug discovery and development.</p>","PeriodicalId":19530,"journal":{"name":"Omics A Journal of Integrative Biology","volume":" ","pages":"60-71"},"PeriodicalIF":2.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}