FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2114323702> ?p ?o ?g. }

• W2114323702 endingPage "6493" @default.
• W2114323702 startingPage "6484" @default.
• W2114323702 abstract "Abstract Ribonucleotide reductase (RNR) is an attractive target for anticancer agents given its central function in DNA synthesis, growth, metastasis, and drug resistance of cancer cells. The current clinically established RNR inhibitors have the shortcomings of short half-life, drug resistance, and iron chelation. Here, we report the development of a novel class of effective RNR inhibitors addressing these issues. A novel ligand-binding pocket on the RNR small subunit (RRM2) near the C-terminal tail was proposed by computer modeling and verified by site-directed mutagenesis and nuclear magnetic resonance (NMR) techniques. A compound targeting this pocket was identified by virtual screening of the National Cancer Institute (NCI) diverse small-molecule database. By lead optimization, we developed the novel RNR inhibitor COH29 that acted as a potent inhibitor of both recombinant and cellular human RNR enzymes. COH29 overcame hydroxyurea and gemcitabine resistance in cancer cells. It effectively inhibited proliferation of most cell lines in the NCI 60 human cancer panel, most notably ovarian cancer and leukemia, but exerted little effect on normal fibroblasts or endothelial cells. In mouse xenograft models of human cancer, COH29 treatment reduced tumor growth compared with vehicle. Site-directed mutagenesis, NMR, and surface plasmon resonance biosensor studies confirmed COH29 binding to the proposed ligand-binding pocket and offered evidence for assembly blockade of the RRM1-RRM2 quaternary structure. Our findings offer preclinical validation of COH29 as a promising new class of RNR inhibitors with a new mechanism of inhibition, with broad potential for improved treatment of human cancer. Cancer Res; 73(21); 6484–93. ©2013 AACR." @default.
• W2114323702 created "2016-06-24" @default.
• W2114323702 creator A5002803374 @default.
• W2114323702 creator A5002940955 @default.
• W2114323702 creator A5009104622 @default.
• W2114323702 creator A5014173403 @default.
• W2114323702 creator A5031383858 @default.
• W2114323702 creator A5032401248 @default.
• W2114323702 creator A5039384923 @default.
• W2114323702 creator A5047650310 @default.
• W2114323702 creator A5047679990 @default.
• W2114323702 creator A5048401428 @default.
• W2114323702 creator A5054078700 @default.
• W2114323702 creator A5075374559 @default.
• W2114323702 date "2013-10-31" @default.
• W2114323702 modified "2023-10-15" @default.
• W2114323702 title "A Small-Molecule Blocking Ribonucleotide Reductase Holoenzyme Formation Inhibits Cancer Cell Growth and Overcomes Drug Resistance" @default.
• W2114323702 cites W105526937 @default.
• W2114323702 cites W1680634601 @default.
• W2114323702 cites W1986305567 @default.
• W2114323702 cites W1986462630 @default.
• W2114323702 cites W1989238401 @default.
• W2114323702 cites W1990551485 @default.
• W2114323702 cites W2000189967 @default.
• W2114323702 cites W2002551641 @default.
• W2114323702 cites W2019227458 @default.
• W2114323702 cites W2023282013 @default.
• W2114323702 cites W2024763149 @default.
• W2114323702 cites W2040157581 @default.
• W2114323702 cites W2043530257 @default.
• W2114323702 cites W2046020180 @default.
• W2114323702 cites W2047167565 @default.
• W2114323702 cites W2050507823 @default.
• W2114323702 cites W2054740290 @default.
• W2114323702 cites W2055810949 @default.
• W2114323702 cites W2061151008 @default.
• W2114323702 cites W2066969026 @default.
• W2114323702 cites W2068973845 @default.
• W2114323702 cites W2073347601 @default.
• W2114323702 cites W2074611661 @default.
• W2114323702 cites W2082820112 @default.
• W2114323702 cites W2087042075 @default.
• W2114323702 cites W2087913780 @default.
• W2114323702 cites W2089440451 @default.
• W2114323702 cites W2103041841 @default.
• W2114323702 cites W2112481981 @default.
• W2114323702 cites W2114779636 @default.
• W2114323702 cites W2143391022 @default.
• W2114323702 cites W2154684019 @default.
• W2114323702 cites W2224915174 @default.
• W2114323702 cites W4248412843 @default.
• W2114323702 cites W4252954754 @default.
• W2114323702 doi "https://doi.org/10.1158/0008-5472.can-13-1094" @default.
• W2114323702 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3823501" @default.
• W2114323702 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/24072748" @default.
• W2114323702 hasPublicationYear "2013" @default.
• W2114323702 type Work @default.
• W2114323702 sameAs 2114323702 @default.
• W2114323702 citedByCount "59" @default.
• W2114323702 countsByYear W21143237022014 @default.
• W2114323702 countsByYear W21143237022015 @default.
• W2114323702 countsByYear W21143237022016 @default.
• W2114323702 countsByYear W21143237022017 @default.
• W2114323702 countsByYear W21143237022018 @default.
• W2114323702 countsByYear W21143237022019 @default.
• W2114323702 countsByYear W21143237022020 @default.
• W2114323702 countsByYear W21143237022021 @default.
• W2114323702 countsByYear W21143237022022 @default.
• W2114323702 countsByYear W21143237022023 @default.
• W2114323702 crossrefType "journal-article" @default.
• W2114323702 hasAuthorship W2114323702A5002803374 @default.
• W2114323702 hasAuthorship W2114323702A5002940955 @default.
• W2114323702 hasAuthorship W2114323702A5009104622 @default.
• W2114323702 hasAuthorship W2114323702A5014173403 @default.
• W2114323702 hasAuthorship W2114323702A5031383858 @default.
• W2114323702 hasAuthorship W2114323702A5032401248 @default.
• W2114323702 hasAuthorship W2114323702A5039384923 @default.
• W2114323702 hasAuthorship W2114323702A5047650310 @default.
• W2114323702 hasAuthorship W2114323702A5047679990 @default.
• W2114323702 hasAuthorship W2114323702A5048401428 @default.
• W2114323702 hasAuthorship W2114323702A5054078700 @default.
• W2114323702 hasAuthorship W2114323702A5075374559 @default.
• W2114323702 hasBestOaLocation W21143237021 @default.
• W2114323702 hasConcept C104292427 @default.
• W2114323702 hasConcept C104317684 @default.
• W2114323702 hasConcept C121608353 @default.
• W2114323702 hasConcept C161624437 @default.
• W2114323702 hasConcept C16318435 @default.
• W2114323702 hasConcept C185592680 @default.
• W2114323702 hasConcept C4710235 @default.
• W2114323702 hasConcept C501734568 @default.
• W2114323702 hasConcept C502942594 @default.
• W2114323702 hasConcept C54355233 @default.
• W2114323702 hasConcept C55493867 @default.
• W2114323702 hasConcept C62112901 @default.
• W2114323702 hasConcept C74187038 @default.
• W2114323702 hasConcept C86803240 @default.
• W2114323702 hasConcept C96232424 @default.

• next