{"title":"通过网络生物学、药物再利用和虚拟筛选策略,探索胃癌的潜在生物标志物和先导分子。","authors":"Sagarika Saha, Sanket Bapat, Durairaj Vijayasarathi, Renu Vyas","doi":"10.1007/s11030-024-10995-6","DOIUrl":null,"url":null,"abstract":"<p><p>Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.</p>","PeriodicalId":708,"journal":{"name":"Molecular Diversity","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.\",\"authors\":\"Sagarika Saha, Sanket Bapat, Durairaj Vijayasarathi, Renu Vyas\",\"doi\":\"10.1007/s11030-024-10995-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.</p>\",\"PeriodicalId\":708,\"journal\":{\"name\":\"Molecular Diversity\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-09-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Diversity\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1007/s11030-024-10995-6\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, APPLIED\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Diversity","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1007/s11030-024-10995-6","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}
Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.
Gastric cancer poses a significant global health challenge, necessitating innovative approaches for biomarker discovery and therapeutic intervention. This study employs a multifaceted strategy integrating network biology, drug repurposing, and virtual screening to elucidate and expand the molecular landscape of gastric cancer. We identified and prioritized key genes implicated in gastric cancer by utilizing data from diverse databases and text-mining techniques. Network analysis underscored intricate gene interactions, emphasizing potential therapeutic targets such as CTNNB1, BCL2, TP53, etc, and highlighted ACTB among the top hub genes crucial in disease progression. Drug repurposing on 626 FDA-approved drugs for digestive system-related cancers revealed Norgestimate and Nimesulide as likely top candidates for gastric cancer, validated by molecular docking and dynamics simulations. Further, combinatorial synthesis of scaffold libraries derived from known chemotypes generated 56,160 virtual compounds, of which 76 new compounds were prioritized based on promising binding affinities and interactions at critical residues. Hotspot residue analysis identified GLU 214 and others as essential for ligand binding stability, enhancing compound efficacy and specificity. These findings support the therapeutic potential of targeting beta-actin protein in gastric cancer treatment, suggesting a future for further experimental validation and clinical translation. In conclusion, this study highlights the potential of repurposable drugs and virtual screening which can be used in combination with existing anti-gastric cancer drugs for gastric cancer therapy, emphasizing the role of computational methodologies in drug discovery.
期刊介绍:
Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including:
combinatorial chemistry and parallel synthesis;
small molecule libraries;
microwave synthesis;
flow synthesis;
fluorous synthesis;
diversity oriented synthesis (DOS);
nanoreactors;
click chemistry;
multiplex technologies;
fragment- and ligand-based design;
structure/function/SAR;
computational chemistry and molecular design;
chemoinformatics;
screening techniques and screening interfaces;
analytical and purification methods;
robotics, automation and miniaturization;
targeted libraries;
display libraries;
peptides and peptoids;
proteins;
oligonucleotides;
carbohydrates;
natural diversity;
new methods of library formulation and deconvolution;
directed evolution, origin of life and recombination;
search techniques, landscapes, random chemistry and more;