Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design
LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. S...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-01-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/1/24 |
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| author | Ningying Zheng Xuan Li Nan Zhou Lianxiang Luo |
| author_facet | Ningying Zheng Xuan Li Nan Zhou Lianxiang Luo |
| author_sort | Ningying Zheng |
| collection | DOAJ |
| description | LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. Six compounds were optimized for protein binding after being docked against the positive control Compound A. Two compounds showed promising results in ADMET screening. Molecular dynamics simulations were utilized to predict binding mechanisms, with Compound 69081_50 identified as a potential LCN2 inhibitor. MM-PBSA analysis revealed key amino acid residues that are involved in interactions, suggesting that Compound 69081_50 could be a candidate for drug development. |
| format | Article |
| id | doaj-art-a3a7abe49c8c47179c1a52f102e6b83b |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj-art-a3a7abe49c8c47179c1a52f102e6b83b2025-01-24T13:39:31ZengMDPI AGMarine Drugs1660-33972025-01-012312410.3390/md23010024Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment DesignNingying Zheng0Xuan Li1Nan Zhou2Lianxiang Luo3The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang 524023, ChinaThe Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang 524023, ChinaLCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. Six compounds were optimized for protein binding after being docked against the positive control Compound A. Two compounds showed promising results in ADMET screening. Molecular dynamics simulations were utilized to predict binding mechanisms, with Compound 69081_50 identified as a potential LCN2 inhibitor. MM-PBSA analysis revealed key amino acid residues that are involved in interactions, suggesting that Compound 69081_50 could be a candidate for drug development.https://www.mdpi.com/1660-3397/23/1/24marine natural compoundsLCN2pharmacophore modelingscaffold hoppingvirtual screeningmolecular dynamics simulation |
| spellingShingle | Ningying Zheng Xuan Li Nan Zhou Lianxiang Luo Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design Marine Drugs marine natural compounds LCN2 pharmacophore modeling scaffold hopping virtual screening molecular dynamics simulation |
| title | Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design |
| title_full | Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design |
| title_fullStr | Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design |
| title_full_unstemmed | Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design |
| title_short | Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design |
| title_sort | identification of novel lcn2 inhibitors based on construction of pharmacophore models and screening of marine compound libraries by fragment design |
| topic | marine natural compounds LCN2 pharmacophore modeling scaffold hopping virtual screening molecular dynamics simulation |
| url | https://www.mdpi.com/1660-3397/23/1/24 |
| work_keys_str_mv | AT ningyingzheng identificationofnovellcn2inhibitorsbasedonconstructionofpharmacophoremodelsandscreeningofmarinecompoundlibrariesbyfragmentdesign AT xuanli identificationofnovellcn2inhibitorsbasedonconstructionofpharmacophoremodelsandscreeningofmarinecompoundlibrariesbyfragmentdesign AT nanzhou identificationofnovellcn2inhibitorsbasedonconstructionofpharmacophoremodelsandscreeningofmarinecompoundlibrariesbyfragmentdesign AT lianxiangluo identificationofnovellcn2inhibitorsbasedonconstructionofpharmacophoremodelsandscreeningofmarinecompoundlibrariesbyfragmentdesign |