FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896862105> ?p ?o ?g. }

• W2896862105 abstract "Abstract Targeted protein degradation has arisen as a powerful strategy for drug discovery allowing the targeting of undruggable proteins for proteasomal degradation. This approach most often employs heterobifunctional degraders consisting of a protein-targeting ligand linked to an E3 ligase recruiter to ubiquitinate and mark proteins of interest for proteasomal degradation. One challenge with this approach, however, is that only few E3 ligase recruiters currently exist for targeted protein degradation applications, despite the hundreds of known E3 ligases in the human genome. Here, we utilized activity-based protein profiling (ABPP)-based covalent ligand screening approaches to identify cysteine-reactive small-molecules that react with the E3 ubiquitin ligase RNF4 and provide chemical starting points for the design of RNF4-based degraders. The hit covalent ligand from this screen reacted with either of two zinc-coordinating cysteines in the RING domain, C132 and C135, with no effect on RNF4 activity. We further optimized the potency of this hit and incorporated this potential RNF4 recruiter into a bifunctional degrader linked to JQ1, an inhibitor of the BET family of bromodomain proteins. We demonstrate that the resulting compound CCW 28-3 is capable of degrading BRD4 in a proteasome- and RNF4-dependent manner. In this study, we have shown the feasibility of using chemoproteomics-enabled covalent ligand screening platforms to expand the scope of E3 ligase recruiters that can be exploited for targeted protein degradation applications." @default.
• W2896862105 created "2018-10-26" @default.
• W2896862105 creator A5001174927 @default.
• W2896862105 creator A5005136916 @default.
• W2896862105 creator A5006914326 @default.
• W2896862105 creator A5006947389 @default.
• W2896862105 creator A5021694845 @default.
• W2896862105 creator A5031380030 @default.
• W2896862105 creator A5035184259 @default.
• W2896862105 creator A5041835523 @default.
• W2896862105 creator A5042256754 @default.
• W2896862105 creator A5044400776 @default.
• W2896862105 creator A5062067947 @default.
• W2896862105 date "2018-10-16" @default.
• W2896862105 modified "2023-09-25" @default.
• W2896862105 title "Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications" @default.
• W2896862105 cites W1546153538 @default.
• W2896862105 cites W1565539350 @default.
• W2896862105 cites W1845308957 @default.
• W2896862105 cites W1964736119 @default.
• W2896862105 cites W1964900033 @default.
• W2896862105 cites W1970833825 @default.
• W2896862105 cites W1976509033 @default.
• W2896862105 cites W1984881591 @default.
• W2896862105 cites W1995770177 @default.
• W2896862105 cites W2018339027 @default.
• W2896862105 cites W2023935690 @default.
• W2896862105 cites W2041535798 @default.
• W2896862105 cites W2053943711 @default.
• W2896862105 cites W2066559144 @default.
• W2896862105 cites W2071737169 @default.
• W2896862105 cites W2083469632 @default.
• W2896862105 cites W2097933346 @default.
• W2896862105 cites W2119126606 @default.
• W2896862105 cites W2126593560 @default.
• W2896862105 cites W2128738080 @default.
• W2896862105 cites W2133639841 @default.
• W2896862105 cites W2139896493 @default.
• W2896862105 cites W2182963873 @default.
• W2896862105 cites W2227431445 @default.
• W2896862105 cites W2287686703 @default.
• W2896862105 cites W2357535822 @default.
• W2896862105 cites W2430132928 @default.
• W2896862105 cites W2553908226 @default.
• W2896862105 cites W2586539307 @default.
• W2896862105 cites W2588493231 @default.
• W2896862105 cites W2588760275 @default.
• W2896862105 cites W2596709339 @default.
• W2896862105 cites W2597078857 @default.
• W2896862105 cites W2742118221 @default.
• W2896862105 cites W2743800043 @default.
• W2896862105 cites W2749269113 @default.
• W2896862105 cites W2754208640 @default.
• W2896862105 cites W2755830996 @default.
• W2896862105 cites W2755866416 @default.
• W2896862105 cites W2806672448 @default.
• W2896862105 cites W2883857562 @default.
• W2896862105 cites W2885955030 @default.
• W2896862105 cites W4232534952 @default.
• W2896862105 doi "https://doi.org/10.1101/439125" @default.
• W2896862105 hasPublicationYear "2018" @default.
• W2896862105 type Work @default.
• W2896862105 sameAs 2896862105 @default.
• W2896862105 citedByCount "2" @default.
• W2896862105 countsByYear W28968621052019 @default.
• W2896862105 countsByYear W28968621052021 @default.
• W2896862105 crossrefType "posted-content" @default.
• W2896862105 hasAuthorship W2896862105A5001174927 @default.
• W2896862105 hasAuthorship W2896862105A5005136916 @default.
• W2896862105 hasAuthorship W2896862105A5006914326 @default.
• W2896862105 hasAuthorship W2896862105A5006947389 @default.
• W2896862105 hasAuthorship W2896862105A5021694845 @default.
• W2896862105 hasAuthorship W2896862105A5031380030 @default.
• W2896862105 hasAuthorship W2896862105A5035184259 @default.
• W2896862105 hasAuthorship W2896862105A5041835523 @default.
• W2896862105 hasAuthorship W2896862105A5042256754 @default.
• W2896862105 hasAuthorship W2896862105A5044400776 @default.
• W2896862105 hasAuthorship W2896862105A5062067947 @default.
• W2896862105 hasBestOaLocation W28968621051 @default.
• W2896862105 hasConcept C104317684 @default.
• W2896862105 hasConcept C116569031 @default.
• W2896862105 hasConcept C134459356 @default.
• W2896862105 hasConcept C138599941 @default.
• W2896862105 hasConcept C140248907 @default.
• W2896862105 hasConcept C170493617 @default.
• W2896862105 hasConcept C175114707 @default.
• W2896862105 hasConcept C185592680 @default.
• W2896862105 hasConcept C24284526 @default.
• W2896862105 hasConcept C25602115 @default.
• W2896862105 hasConcept C27740335 @default.
• W2896862105 hasConcept C2779634854 @default.
• W2896862105 hasConcept C2908868211 @default.
• W2896862105 hasConcept C2992195973 @default.
• W2896862105 hasConcept C552990157 @default.
• W2896862105 hasConcept C55493867 @default.
• W2896862105 hasConcept C64927066 @default.
• W2896862105 hasConcept C70721500 @default.
• W2896862105 hasConcept C74187038 @default.
• W2896862105 hasConcept C74401373 @default.
• W2896862105 hasConcept C86339819 @default.

• next