FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384155005> ?p ?o ?g. }

• W4384155005 endingPage "9822" @default.
• W4384155005 startingPage "9797" @default.
• W4384155005 abstract "In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating of the mutant channel. One of the most promising CF drug targets is the ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, the first ever reported inhibitor of RNF5 was discovered, i.e., the 1,2,4-thiadiazol-5-ylidene inh-2. Here, we designed and synthesized a series of new analogues to explore the structure–activity relationships (SAR) of this class of compounds. SAR efforts ultimately led to compound 16, which showed a greater F508del-CFTR corrector activity than inh-2, good tolerability, and no toxic side effects. Analogue 16 increased the basal level of autophagy similar to what has been described with RNF5 silencing. Furthermore, co-treatment with 16 significantly improved the F508del-CFTR rescue induced by the triple combination elexacaftor/tezacaftor/ivacaftor in CFBE41o– cells. These findings validate the 1,2,4-thiadiazolylidene scaffold for the discovery of novel RNF5 inhibitors and provide evidence to pursue this unprecedented strategy for the treatment of CF." @default.
• W4384155005 created "2023-07-14" @default.
• W4384155005 creator A5000637221 @default.
• W4384155005 creator A5010189561 @default.
• W4384155005 creator A5018522294 @default.
• W4384155005 creator A5021455005 @default.
• W4384155005 creator A5021953983 @default.
• W4384155005 creator A5029940808 @default.
• W4384155005 creator A5030003254 @default.
• W4384155005 creator A5035077656 @default.
• W4384155005 creator A5038859802 @default.
• W4384155005 creator A5042284243 @default.
• W4384155005 creator A5045740482 @default.
• W4384155005 creator A5049519225 @default.
• W4384155005 creator A5050613642 @default.
• W4384155005 creator A5071952535 @default.
• W4384155005 creator A5072224755 @default.
• W4384155005 creator A5080493670 @default.
• W4384155005 date "2023-07-13" @default.
• W4384155005 modified "2023-09-30" @default.
• W4384155005 title "Innovative Strategy toward Mutant CFTR Rescue in Cystic Fibrosis: Design and Synthesis of Thiadiazole Inhibitors of the E3 Ligase RNF5" @default.
• W4384155005 cites W120703973 @default.
• W4384155005 cites W1209134892 @default.
• W4384155005 cites W1505296146 @default.
• W4384155005 cites W1589654967 @default.
• W4384155005 cites W1599366903 @default.
• W4384155005 cites W1677528798 @default.
• W4384155005 cites W1971663775 @default.
• W4384155005 cites W1981737096 @default.
• W4384155005 cites W1984005894 @default.
• W4384155005 cites W1992571797 @default.
• W4384155005 cites W1995203361 @default.
• W4384155005 cites W2035131077 @default.
• W4384155005 cites W2039599894 @default.
• W4384155005 cites W2049914201 @default.
• W4384155005 cites W2052588826 @default.
• W4384155005 cites W2058169488 @default.
• W4384155005 cites W2061044370 @default.
• W4384155005 cites W2063641892 @default.
• W4384155005 cites W2070043042 @default.
• W4384155005 cites W2071407356 @default.
• W4384155005 cites W2072945029 @default.
• W4384155005 cites W2075257287 @default.
• W4384155005 cites W2076159058 @default.
• W4384155005 cites W2079234445 @default.
• W4384155005 cites W2087925988 @default.
• W4384155005 cites W2088150218 @default.
• W4384155005 cites W2090953360 @default.
• W4384155005 cites W2107557685 @default.
• W4384155005 cites W2115046089 @default.
• W4384155005 cites W2139574393 @default.
• W4384155005 cites W2147285875 @default.
• W4384155005 cites W2151230734 @default.
• W4384155005 cites W2151837778 @default.
• W4384155005 cites W2161007540 @default.
• W4384155005 cites W2164926713 @default.
• W4384155005 cites W2169175289 @default.
• W4384155005 cites W2269507537 @default.
• W4384155005 cites W2301131921 @default.
• W4384155005 cites W2564832387 @default.
• W4384155005 cites W2606486957 @default.
• W4384155005 cites W2754849847 @default.
• W4384155005 cites W2765825922 @default.
• W4384155005 cites W2777476097 @default.
• W4384155005 cites W2799988929 @default.
• W4384155005 cites W2802538969 @default.
• W4384155005 cites W2887536211 @default.
• W4384155005 cites W2897626245 @default.
• W4384155005 cites W2911461986 @default.
• W4384155005 cites W2915880121 @default.
• W4384155005 cites W2951910473 @default.
• W4384155005 cites W2959193061 @default.
• W4384155005 cites W2972023953 @default.
• W4384155005 cites W2977573849 @default.
• W4384155005 cites W2982296199 @default.
• W4384155005 cites W2991507921 @default.
• W4384155005 cites W3015162743 @default.
• W4384155005 cites W3015348801 @default.
• W4384155005 cites W3043517438 @default.
• W4384155005 cites W3081438953 @default.
• W4384155005 cites W3161541109 @default.
• W4384155005 cites W4223555313 @default.
• W4384155005 cites W4223969120 @default.
• W4384155005 cites W4294992452 @default.
• W4384155005 doi "https://doi.org/10.1021/acs.jmedchem.3c00608" @default.
• W4384155005 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37440686" @default.
• W4384155005 hasPublicationYear "2023" @default.
• W4384155005 type Work @default.
• W4384155005 citedByCount "1" @default.
• W4384155005 countsByYear W43841550052023 @default.
• W4384155005 crossrefType "journal-article" @default.
• W4384155005 hasAuthorship W4384155005A5000637221 @default.
• W4384155005 hasAuthorship W4384155005A5010189561 @default.
• W4384155005 hasAuthorship W4384155005A5018522294 @default.
• W4384155005 hasAuthorship W4384155005A5021455005 @default.
• W4384155005 hasAuthorship W4384155005A5021953983 @default.
• W4384155005 hasAuthorship W4384155005A5029940808 @default.
• W4384155005 hasAuthorship W4384155005A5030003254 @default.

• next