Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 류성언 | - |
dc.date.accessioned | 2022-05-26T01:47:35Z | - |
dc.date.available | 2022-05-26T01:47:35Z | - |
dc.date.issued | 2020-10 | - |
dc.identifier.citation | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, no. 21, article no. 7878 | en_US |
dc.identifier.issn | 1422-0067 | - |
dc.identifier.uri | https://www.mdpi.com/1422-0067/21/21/7878 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/171184 | - |
dc.description.abstract | Aberrant tyrosine-protein kinase Mer (MerTK) expression triggers prosurvival signaling and contributes to cell survival, invasive motility, and chemoresistance in many kinds of cancers. In addition, recent reports suggested that MerTK could be a primary target for abnormal platelet aggregation. Consequently, MerTK inhibitors may promote cancer cell death, sensitize cells to chemotherapy, and act as new antiplatelet agents. We screened an inhouse chemical library to discover novel small-molecule MerTK inhibitors, and identified AZD7762, which is known as a checkpoint-kinase (Chk) inhibitor. The inhibition of MerTK by AZD7762 was validated using an in vitro homogeneous time-resolved fluorescence (HTRF) assay and through monitoring the decrease in phosphorylated MerTK in two lung cancer cell lines. We also determined the crystal structure of the MerTK:AZD7762 complex and revealed the binding mode of AZD7762 to MerTK. Structural information from the MerTK:AZD7762 complex and its comparison with other MerTK:inhibitor structures gave us new insights for optimizing the development of inhibitors targeting MerTK. | en_US |
dc.description.sponsorship | This study was funded by National Cancer Center Korea (1910031) and National Research Foundation of Korea (NRF) grants from the Korean government (MSIT) (NRF-2018R1A5A2023127 and NRF-2019R1A2C1002545) to B.I.L. | en_US |
dc.language.iso | en | en_US |
dc.publisher | MDPI | en_US |
dc.subject | MerTK | en_US |
dc.subject | AZD7762 | en_US |
dc.subject | TAM family kinase | en_US |
dc.subject | X-ray crystallography | en_US |
dc.title | Crystal Structure of the Kinase Domain of MerTK in Complex with AZD7762 Provides Clues for Structure-Based Drug Development | en_US |
dc.type | Article | en_US |
dc.relation.no | 21 | - |
dc.relation.volume | 21 | - |
dc.identifier.doi | 10.3390/ijms21217878 | - |
dc.relation.page | 7878-7878 | - |
dc.relation.journal | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | - |
dc.contributor.googleauthor | Park, Tae Hyun | - |
dc.contributor.googleauthor | Bae, Seung-Hyun | - |
dc.contributor.googleauthor | Bong, Seoung Min | - |
dc.contributor.googleauthor | Ryu, Seong Eon | - |
dc.contributor.googleauthor | Jang, Hyonchol | - |
dc.contributor.googleauthor | Lee, Byung Il | - |
dc.relation.code | 2020050347 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF ENGINEERING[S] | - |
dc.sector.department | DEPARTMENT OF BIOENGINEERING | - |
dc.identifier.pid | ryuse | - |
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