Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1
DC Field | Value | Language |
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dc.contributor.author | Hakami, Mohammed Ageeli | - |
dc.contributor.author | Alotaibi, Bader S. | - |
dc.contributor.author | Alkhalil, Samia S. | - |
dc.contributor.author | Anwar, Saleha | - |
dc.contributor.author | Jairajpuri, Deeba Shamim | - |
dc.contributor.author | Hazazi, Ali | - |
dc.contributor.author | Alsulami, Mishal Olayan | - |
dc.contributor.author | Jawaid, Talha | - |
dc.contributor.author | Yadav, Dharmendra Kumar | - |
dc.contributor.author | Almasoudi, Hassan H. | - |
dc.date.accessioned | 2024-04-26T13:00:21Z | - |
dc.date.available | 2024-04-26T13:00:21Z | - |
dc.date.issued | 2024-03 | - |
dc.identifier.issn | 0141-8130 | - |
dc.identifier.issn | 1879-0003 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/91053 | - |
dc.description.abstract | Integrin-linked kinase (ILK), a beta 1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M-1) values of 1.9 x 10(5), 3.6 x 10(5), and 4.0 x 10(5) and triangle G(0) values (kcal/mol) -6.19554, -7.8557 and -8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of -6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 x 10(5) M-1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of similar to 5.23 mu M). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ELSEVIER | - |
dc.title | Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1 | - |
dc.type | Article | - |
dc.identifier.wosid | 001188776900001 | - |
dc.identifier.doi | 10.1016/j.ijbiomac.2024.130146 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, v.262 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85185825124 | - |
dc.citation.title | INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES | - |
dc.citation.volume | 262 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | Neuroinflammation | - |
dc.subject.keywordAuthor | Protein kinase | - |
dc.subject.keywordAuthor | Natural products | - |
dc.subject.keywordAuthor | Drug discovery | - |
dc.subject.keywordAuthor | Cancer therapeutics | - |
dc.subject.keywordAuthor | Enzyme inhibition | - |
dc.subject.keywordPlus | EPITHELIAL-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | ANTICANCER ACTIVITY | - |
dc.subject.keywordPlus | LIGAND-BINDING | - |
dc.subject.keywordPlus | E-CADHERIN | - |
dc.subject.keywordPlus | ILK | - |
dc.subject.keywordPlus | OVEREXPRESSION | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.subject.keywordPlus | INVASION | - |
dc.subject.keywordPlus | PH | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Polymer Science | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Applied | - |
dc.relation.journalWebOfScienceCategory | Polymer Science | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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