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http://dx.doi.org/10.25673/115381
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DC Element | Wert | Sprache |
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dc.contributor.author | Alfayomy, Abdallah M. | - |
dc.contributor.author | Ashry, Ramy | - |
dc.contributor.author | Kansy, Anita G. | - |
dc.contributor.author | Sarnow, Anne-Christin | - |
dc.contributor.author | Erdmann, Frank | - |
dc.contributor.author | Schmidt, Matthias | - |
dc.contributor.author | Krämer, Oliver Holger | - |
dc.contributor.author | Sippl, Wolfgang | - |
dc.date.accessioned | 2024-03-19T07:15:58Z | - |
dc.date.available | 2024-03-19T07:15:58Z | - |
dc.date.issued | 2024 | - |
dc.identifier.uri | https://opendata.uni-halle.de//handle/1981185920/117335 | - |
dc.identifier.uri | http://dx.doi.org/10.25673/115381 | - |
dc.description.abstract | The Ataxia telangiectasia and RAD3-related (ATR) kinase is a key regulator of DNA replication stress responses and DNA-damage checkpoints. Several potent and selective ATR inhibitors are reported and four of them are currently in clinical trials in combination with radio- or chemotherapy. Based on the idea of degrading target proteins rather than inhibiting them, we designed, synthesized and biologically characterized a library of ATR-targeted proteolysis targeting chimera (PROTACs). Among the synthesized compounds, the lenalidomide-based PROTAC 42i was the most promising. In pancreatic and cervix cancer cells cancer cells, it reduced ATR to 40 % of the levels in untreated cells. 42i selectively degraded ATR through the proteasome, dependent on the E3 ubiquitin ligase component cereblon, and without affecting the associated kinases ATM and DNA-PKcs. 42i may be a promising candidate for further optimization and biological characterization in various cancer cells. | eng |
dc.language.iso | eng | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | - |
dc.subject.ddc | 615 | - |
dc.title | Design, synthesis, and biological characterization of proteolysis targeting chimera (PROTACs) for the ataxia telangiectasia and RAD3-related (ATR) kinase | eng |
dc.type | Article | - |
local.versionType | publishedVersion | - |
local.bibliographicCitation.journaltitle | European journal of medicinal chemistry | - |
local.bibliographicCitation.volume | 267 | - |
local.bibliographicCitation.publishername | Elsevier Science | - |
local.bibliographicCitation.publisherplace | Amsterdam [u.a.] | - |
local.bibliographicCitation.doi | 10.1016/j.ejmech.2024.116167 | - |
local.subject.keywords | Ataxia telangiectasia and RAD3-Related (ATR) kinase, Proteolysis targeting chimera (PROTAC), Protein degradation, Synthesis, MIA PaCa-2 | - |
local.openaccess | true | - |
dc.identifier.ppn | 1881317587 | - |
cbs.publication.displayform | 2024 | - |
local.bibliographicCitation.year | 2024 | - |
cbs.sru.importDate | 2024-03-19T07:15:36Z | - |
local.bibliographicCitation | Enthalten in European journal of medicinal chemistry - Amsterdam [u.a.] : Elsevier Science, 1987 | - |
local.accessrights.dnb | free | - |
Enthalten in den Sammlungen: | Open Access Publikationen der MLU |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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1-s2.0-S0223523424000473-main.pdf | 6 MB | Adobe PDF | ![]() Öffnen/Anzeigen |