Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1
<p dir="ltr">Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpr...
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2023
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| _version_ | 1864513507535355904 |
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| author | Mohammad Molla (19467889) |
| author2 | Mohammed Aljahdali (19467892) Md Sumon (19467895) Amer Asseri (19467898) Hisham Altayb (16299020) Md. Islam (3413852) Ahad Alsaiari (19467901) F. Opo (19467904) Nushrat Jahan (19467907) Foysal Ahammad (9286524) Farhan Mohammad (256409) |
| author2_role | author author author author author author author author author author |
| author_facet | Mohammad Molla (19467889) Mohammed Aljahdali (19467892) Md Sumon (19467895) Amer Asseri (19467898) Hisham Altayb (16299020) Md. Islam (3413852) Ahad Alsaiari (19467901) F. Opo (19467904) Nushrat Jahan (19467907) Foysal Ahammad (9286524) Farhan Mohammad (256409) |
| author_role | author |
| dc.creator.none.fl_str_mv | Mohammad Molla (19467889) Mohammed Aljahdali (19467892) Md Sumon (19467895) Amer Asseri (19467898) Hisham Altayb (16299020) Md. Islam (3413852) Ahad Alsaiari (19467901) F. Opo (19467904) Nushrat Jahan (19467907) Foysal Ahammad (9286524) Farhan Mohammad (256409) |
| dc.date.none.fl_str_mv | 2023-01-13T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3390/ph16010120 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Integrative_Ligand-Based_Pharmacophore_Modeling_Virtual_Screening_and_Molecular_Docking_Simulation_Approaches_Identified_Potential_Lead_Compounds_against_Pancreatic_Cancer_by_Targeting_FAK1/26808466 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences pancreatic cancer FAK1 protein ligand-based pharmacophore drug design purchasable compounds molecular docking ADMET MD simulation MM-GBSA |
| dc.title.none.fl_str_mv | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of −10.4, −10.1, and −9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceuticals<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ph16010120" target="_blank">https://dx.doi.org/10.3390/ph16010120</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_0955afd2bb1353d82fb9c324924f81af |
| identifier_str_mv | 10.3390/ph16010120 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26808466 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1Mohammad Molla (19467889)Mohammed Aljahdali (19467892)Md Sumon (19467895)Amer Asseri (19467898)Hisham Altayb (16299020)Md. Islam (3413852)Ahad Alsaiari (19467901)F. Opo (19467904)Nushrat Jahan (19467907)Foysal Ahammad (9286524)Farhan Mohammad (256409)Biomedical and clinical sciencesClinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencespancreatic cancerFAK1 proteinligand-based pharmacophore drug designpurchasable compoundsmolecular dockingADMETMD simulationMM-GBSA<p dir="ltr">Pancreatic cancer is a very deadly disease with a 5-year survival rate, making it one of the leading causes of cancer-related deaths globally. Focal adhesion kinase 1 (FAK1) is a ubiquitously expressed protein in pancreatic cancer. FAK, a tyrosine kinase that is overexpressed in cancer cells, is crucial for the development of tumors into malignant phenotypes. FAK functions in response to extracellular signals by triggering transmembrane receptor signaling, which enhances focal adhesion turnover, cell adhesion, cell migration, and gene expression. The ligand-based drug design approach was used to identify potential compounds against the target protein, which included molecular docking: ADME (absorption, distribution, metabolism, and excretion), toxicity, molecular dynamics (MD) simulation, and molecular mechanics generalized born surface area (MM-GBSA). Following the retrieval of twenty hits, four compounds were selected for further evaluation based on a molecular docking approach. Three newly discovered compounds, including PubChem CID24601203, CID1893370, and CID16355541, with binding scores of −10.4, −10.1, and −9.7 kcal/mol, respectively, may serve as lead compounds for the treatment of pancreatic cancer associated with FAK1. The ADME (absorption, distribution, metabolism, and excretion) and toxicity analyses demonstrated that the compounds were effective and nontoxic. However, further wet laboratory investigations are required to evaluate the activity of the drugs against the cancer.</p><h2>Other Information</h2><p dir="ltr">Published in: Pharmaceuticals<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ph16010120" target="_blank">https://dx.doi.org/10.3390/ph16010120</a></p>2023-01-13T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ph16010120https://figshare.com/articles/journal_contribution/Integrative_Ligand-Based_Pharmacophore_Modeling_Virtual_Screening_and_Molecular_Docking_Simulation_Approaches_Identified_Potential_Lead_Compounds_against_Pancreatic_Cancer_by_Targeting_FAK1/26808466CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/268084662023-01-13T09:00:00Z |
| spellingShingle | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 Mohammad Molla (19467889) Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences pancreatic cancer FAK1 protein ligand-based pharmacophore drug design purchasable compounds molecular docking ADMET MD simulation MM-GBSA |
| status_str | publishedVersion |
| title | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| title_full | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| title_fullStr | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| title_full_unstemmed | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| title_short | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| title_sort | Integrative Ligand-Based Pharmacophore Modeling, Virtual Screening, and Molecular Docking Simulation Approaches Identified Potential Lead Compounds against Pancreatic Cancer by Targeting FAK1 |
| topic | Biomedical and clinical sciences Clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences pancreatic cancer FAK1 protein ligand-based pharmacophore drug design purchasable compounds molecular docking ADMET MD simulation MM-GBSA |