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Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.

التفاصيل البيبلوغرافية
العنوان: Potential inhibitors of VEGFR1, VEGFR2, and VEGFR3 developed through Deep Learning for the treatment of Cervical Cancer.
المؤلفون: Nayarisseri A; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India. anuraj@eminentbio.com.; Bioinformatics Research Laboratory, LeGene Biosciences Pvt Ltd, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India. anuraj@eminentbio.com., Abdalla M; Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Cultural West Road, Jinan, 250012, Shandong Province, People's Republic of China., Joshi I; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India., Yadav M; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India., Bhrdwaj A; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India.; Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630003, India., Chopra I; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India.; School of Medicine and Health Sciences, The George Washington University, Ross Hall, 2300 Eye Street, Washington, D.C., NW, 20037, USA., Khan A; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India.; Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630003, India., Saxena A; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India., Sharma K; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India.; Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630003, India., Panicker A; In silico Research Laboratory, Eminent Biosciences, 91, Sector-A, Mahalakshmi Nagar, Indore, Madhya Pradesh, 452010, India., Panwar U; Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630003, India., Mendonça Junior FJB; Laboratory of Synthesis and Drug Delivery, Department of Biological Sciences, State University of Paraiba, João Pessoa, 58429-500, Brazil., Singh SK; Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu, 630003, India. skysanjeev@gmail.com.
المصدر: Scientific reports [Sci Rep] 2024 Jun 10; Vol. 14 (1), pp. 13251. Date of Electronic Publication: 2024 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Vascular Endothelial Growth Factor Receptor-3*/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-3*/metabolism , Vascular Endothelial Growth Factor Receptor-2*/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2*/metabolism , Uterine Cervical Neoplasms*/drug therapy , Uterine Cervical Neoplasms*/metabolism , Uterine Cervical Neoplasms*/virology , Vascular Endothelial Growth Factor Receptor-1*/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-1*/metabolism , Molecular Docking Simulation* , Deep Learning*, Humans ; Female ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/chemistry
مستخلص: Cervical cancer stands as a prevalent gynaecologic malignancy affecting women globally, often linked to persistent human papillomavirus infection. Biomarkers associated with cervical cancer, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, and VEGF-E, show upregulation and are linked to angiogenesis and lymphangiogenesis. This research aims to employ in-silico methods to target tyrosine kinase receptor proteins-VEGFR-1, VEGFR-2, and VEGFR-3, and identify novel inhibitors for Vascular Endothelial Growth Factors receptors (VEGFRs). A comprehensive literary study was conducted which identified 26 established inhibitors for VEGFR-1, VEGFR-2, and VEGFR-3 receptor proteins. Compounds with high-affinity scores, including PubChem ID-25102847, 369976, and 208908 were chosen from pre-existing compounds for creating Deep Learning-based models. RD-Kit, a Deep learning algorithm, was used to generate 43 million compounds for VEGFR-1, VEGFR-2, and VEGFR-3 targets. Molecular docking studies were conducted on the top 10 molecules for each target to validate the receptor-ligand binding affinity. The results of Molecular Docking indicated that PubChem IDs-71465,645 and 11152946 exhibited strong affinity, designating them as the most efficient molecules. To further investigate their potential, a Molecular Dynamics Simulation was performed to assess conformational stability, and a pharmacophore analysis was also conducted for indoctrinating interactions.
(© 2024. The Author(s).)
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فهرسة مساهمة: Keywords: ADMET studies; Deep learning; Machine-learning; Molecular docking; Molecular dynamics simulation; Python; R programming; VEGFR inhibitors
المشرفين على المادة: EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-3)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1)
EC 2.7.10.1 (KDR protein, human)
0 (Protein Kinase Inhibitors)
EC 2.7.10.1 (FLT4 protein, human)
تواريخ الأحداث: Date Created: 20240610 Date Completed: 20240610 Latest Revision: 20240620
رمز التحديث: 20240620
مُعرف محوري في PubMed: PMC11164920
DOI: 10.1038/s41598-024-63762-w
PMID: 38858458
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-63762-w