DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lim, Sang Min | ko |
dc.contributor.author | Jeong, Yujeong | ko |
dc.contributor.author | Lee, Suhyun | ko |
dc.contributor.author | Im, Honggu | ko |
dc.contributor.author | Tae, Hyun Seop | ko |
dc.contributor.author | Kim, Byung Gyu | ko |
dc.contributor.author | Park, Hee Dong | ko |
dc.contributor.author | Park, Jonghoon | ko |
dc.contributor.author | Hong, Sungwoo | ko |
dc.date.accessioned | 2016-05-16T08:52:10Z | - |
dc.date.available | 2016-05-16T08:52:10Z | - |
dc.date.created | 2015-12-10 | - |
dc.date.created | 2015-12-10 | - |
dc.date.created | 2015-12-10 | - |
dc.date.issued | 2015-11 | - |
dc.identifier.citation | JOURNAL OF MEDICINAL CHEMISTRY, v.58, no.21, pp.8491 - 8502 | - |
dc.identifier.issn | 0022-2623 | - |
dc.identifier.uri | http://hdl.handle.net/10203/207492 | - |
dc.description.abstract | The treatment of activated B cell-like DLBCL (ABC-DLBCL) is one of the urgent unmet medical needs because it is the most resistant DLBCL subtype to current therapies eagerly awaiting effective therapeutic strategies. Recently, the paracaspase MALT1 has emerged as a promising therapeutic target for the treatment of ABC-DLBCL. Herein, we report a new class of MALT1 inhibitors developed by high-throughput screening and structure-based drug design. The original hit, 4-amino-1,2-naphthoquinone series inhibited MALT1 activity but suffered from poor cellular activity. The extensive pharmacophore search led to the discovery of structurally similar beta-lapachone that is a direct inhibitor of MALT1 and possesses favorable physicochemical properties. Molecular simulation studies suggested the possibility of the formation of a covalent bond between MALT1 and, beta-lapachone, which was corroborated by experimental wash-out studies. Inspired by this, we explored the structure activity relationships by incorporating electron-withdrawing substituents at C8 position of beta-lapachone. These MALT1 inhibitors exhibited potent antiproliferative activity to OCI-LY3 cell line and inhibited the cleavage of CYLD mediated MALT1. | - |
dc.language | English | - |
dc.publisher | AMER CHEMICAL SOC | - |
dc.title | Identification of beta-Lapachone Analogs as Novel MALT1 Inhibitors To Treat an Aggressive Subtype of Diffuse Large B-Cell Lymphoma | - |
dc.type | Article | - |
dc.identifier.wosid | 000364796100011 | - |
dc.identifier.scopusid | 2-s2.0-84947460168 | - |
dc.type.rims | ART | - |
dc.citation.volume | 58 | - |
dc.citation.issue | 21 | - |
dc.citation.beginningpage | 8491 | - |
dc.citation.endingpage | 8502 | - |
dc.citation.publicationname | JOURNAL OF MEDICINAL CHEMISTRY | - |
dc.identifier.doi | 10.1021/acs.jmedchem.5b01415 | - |
dc.contributor.localauthor | Hong, Sungwoo | - |
dc.contributor.nonIdAuthor | Lim, Sang Min | - |
dc.contributor.nonIdAuthor | Lee, Suhyun | - |
dc.contributor.nonIdAuthor | Im, Honggu | - |
dc.contributor.nonIdAuthor | Tae, Hyun Seop | - |
dc.contributor.nonIdAuthor | Kim, Byung Gyu | - |
dc.contributor.nonIdAuthor | Park, Hee Dong | - |
dc.contributor.nonIdAuthor | Park, Jonghoon | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | NF-KAPPA-B | - |
dc.subject.keywordPlus | CANCER-CELLS | - |
dc.subject.keywordPlus | ABC-DLBCL | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | KINASE | - |
dc.subject.keywordPlus | PATHOGENESIS | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | DISCOVERY | - |
dc.subject.keywordPlus | PROTEASE | - |
dc.subject.keywordPlus | DESIGN | - |
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