Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 강수성 | * |
dc.date.accessioned | 2020-02-07T16:30:22Z | - |
dc.date.available | 2020-02-07T16:30:22Z | - |
dc.date.issued | 2020 | * |
dc.identifier.issn | 0960-894X | * |
dc.identifier.issn | 1464-3405 | * |
dc.identifier.other | OAK-26332 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/253359 | - |
dc.description.abstract | As the most abundant heat shock protein (HSP), Hsp90 is actively involved in tumor cell growth and various responses to anti-carcinogenic stress. Hsp90 has thus emerged as a potential drug target. A structure-based drug design approach was applied to develop novel resorcinolyltriazole derivatives as Hsp90 inhibitors. Structure-activity relationships (SARs) and molecular docking were investigated to provide a rationale for binding affinity and paralog selectivity. Click chemistry between iodoethynylresorcinol and an azido derivative was used to synthesize a new family of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl) acetates that exhibited Hsp90 binding affinities of 40-100 nM (IC50). Among the synthesized molecules, the triazole alkyl acetates displayed the highest Hsp90 binding affinities. Their potency against Hsp90 was over 100-fold stronger than against TRAP1 and 1-3-fold stronger than against Grp94. In particular, compounds 18, 19, and 30 had Hsp90 inhibitory activities of similar to 45 nM (IC50) and they displayed over 350-fold selectivity for Hsp90 over TRAP1. | * |
dc.language | English | * |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | * |
dc.subject | Hsp90 | * |
dc.subject | TRAP1 | * |
dc.subject | Grp94 | * |
dc.subject | Inhibitor | * |
dc.subject | Selectivity | * |
dc.subject | Resorcinol | * |
dc.subject | Triazole | * |
dc.title | Discovery of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl)acetates as potent Hsp90 inhibitors with selectivity over TRAP1 | * |
dc.type | Article | * |
dc.relation.issue | 2 | * |
dc.relation.volume | 30 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.journaltitle | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | * |
dc.identifier.doi | 10.1016/j.bmcl.2019.126809 | * |
dc.identifier.wosid | WOS:000504873300014 | * |
dc.identifier.scopusid | 2-s2.0-85076516721 | * |
dc.author.google | Jung, Sejin | * |
dc.author.google | Yoon, Nam Gu | * |
dc.author.google | Yang, Sujae | * |
dc.author.google | Kim, Darong | * |
dc.author.google | Lee, Won Seok | * |
dc.author.google | Hong, Ki Bum | * |
dc.author.google | Lee, Changwook | * |
dc.author.google | Kang, Byoung Heon | * |
dc.author.google | Lee, Ji Hoon | * |
dc.author.google | Kang, Soosung | * |
dc.contributor.scopusid | 강수성(56177300500) | * |
dc.date.modifydate | 20240301081003 | * |