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- W4200204518 abstract "DCN1, a co-E3 ligase, interacts with UBC12 and activates cullin-RING ligases (CRLs) by catalyzing cullin neddylation. Although DCN1 has been recognized as an important therapeutic target for human diseases, its role in the cardiovascular area remains unknown. Here, we first found that DCN1 was upregulated in isolated cardiac fibroblasts (CFs) treated by angiotensin (Ang) II and in mouse hearts after pressure overload. Then, structure-based optimizations for DCN1-UBC12 inhibitors were performed based on our previous work, yielding compound DN-2. DN-2 specifically targeted DCN1 at molecular and cellular levels as shown by molecular modeling studies, HTRF, cellular thermal shift and co-immunoprecipitation assays. Importantly, DN-2 effectively reversed Ang II-induced cardiac fibroblast activation, which was associated with the inhibition of cullin 3 neddylation. Our findings indicate a potentially unrecognized role of DCN1 inhibition for anticardiac fibrotic effects. DN-2 may be used as a lead compound for further development." @default.
- W4200204518 created "2021-12-31" @default.
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- W4200204518 date "2021-12-23" @default.
- W4200204518 modified "2023-10-15" @default.
- W4200204518 title "Discovery of Potent and Selective 2-(Benzylthio)pyrimidine-based DCN1-UBC12 Inhibitors for Anticardiac Fibrotic Effects" @default.
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- W4200204518 cites W1964909962 @default.
- W4200204518 cites W1988031203 @default.
- W4200204518 cites W1999353132 @default.
- W4200204518 cites W2004245343 @default.
- W4200204518 cites W2015987375 @default.
- W4200204518 cites W2018041853 @default.
- W4200204518 cites W2018507236 @default.
- W4200204518 cites W2025861321 @default.
- W4200204518 cites W2029133324 @default.
- W4200204518 cites W2031432337 @default.
- W4200204518 cites W2037535298 @default.
- W4200204518 cites W2044172327 @default.
- W4200204518 cites W2048263813 @default.
- W4200204518 cites W2050862994 @default.
- W4200204518 cites W2052472486 @default.
- W4200204518 cites W2055549720 @default.
- W4200204518 cites W2065886910 @default.
- W4200204518 cites W2066787685 @default.
- W4200204518 cites W2068652435 @default.
- W4200204518 cites W2069387298 @default.
- W4200204518 cites W2075720446 @default.
- W4200204518 cites W2076194625 @default.
- W4200204518 cites W2080663210 @default.
- W4200204518 cites W2081027634 @default.
- W4200204518 cites W2083008763 @default.
- W4200204518 cites W2083334037 @default.
- W4200204518 cites W2085006244 @default.
- W4200204518 cites W2085812634 @default.
- W4200204518 cites W2093381148 @default.
- W4200204518 cites W2100835617 @default.
- W4200204518 cites W2110957546 @default.
- W4200204518 cites W2115458617 @default.
- W4200204518 cites W2147993766 @default.
- W4200204518 cites W2149979055 @default.
- W4200204518 cites W2164929494 @default.
- W4200204518 cites W2271736303 @default.
- W4200204518 cites W2292671072 @default.
- W4200204518 cites W2297200517 @default.
- W4200204518 cites W2299099463 @default.
- W4200204518 cites W2323996569 @default.
- W4200204518 cites W2327334027 @default.
- W4200204518 cites W2345719659 @default.
- W4200204518 cites W2563399408 @default.
- W4200204518 cites W2565679277 @default.
- W4200204518 cites W2598014605 @default.
- W4200204518 cites W2608644283 @default.
- W4200204518 cites W2608976820 @default.
- W4200204518 cites W2624254235 @default.
- W4200204518 cites W2765683432 @default.
- W4200204518 cites W2783087879 @default.
- W4200204518 cites W2786247883 @default.
- W4200204518 cites W2792313710 @default.
- W4200204518 cites W2792771883 @default.
- W4200204518 cites W2796866858 @default.
- W4200204518 cites W2850252514 @default.
- W4200204518 cites W2917279229 @default.
- W4200204518 cites W2920551789 @default.
- W4200204518 cites W2948827622 @default.
- W4200204518 cites W2953645345 @default.
- W4200204518 cites W2953832817 @default.
- W4200204518 cites W2967233606 @default.
- W4200204518 cites W2970120506 @default.
- W4200204518 cites W2987774500 @default.
- W4200204518 cites W3044569095 @default.
- W4200204518 cites W3093178094 @default.
- W4200204518 cites W3132520955 @default.
- W4200204518 cites W3137081715 @default.
- W4200204518 cites W3139134653 @default.
- W4200204518 cites W3157333084 @default.
- W4200204518 cites W3162029322 @default.
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- W4200204518 doi "https://doi.org/10.1021/acs.jmedchem.1c01207" @default.
- W4200204518 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34939411" @default.
- W4200204518 hasPublicationYear "2021" @default.
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