From haystack to needle: finding value with DNA encoded library technology at GSK

被引:70
作者
Arico-Muendel, Christopher C. [1 ]
机构
[1] GlaxoSmithKline, 830 Winter St, Waltham, MA 02451 USA
关键词
BCATM INHIBITORS; HIGHLY POTENT; BINDING MODE; IN-VITRO; DISCOVERY; ELT; OPTIMIZATION; ANTAGONISTS; ARYLAMINES; SELECTION;
D O I
10.1039/c6md00341a
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA encoded library technology (ELT) provides access to broad chemical diversity through affinity selection. As an early adopter, GlaxoSmithKline enabled the development of ELT from proof of concept to full fledged contributor to the small molecule therapeutic pipeline. Unique benefits of the GSK incubation include uptake of large numbers of building blocks and privileged scaffolds, guidance on library design, and opportunities to add value beyond lead discovery. Soluble epoxide hydrolase and RIP1 kinase represent two case studies of ELT hits that have advanced into clinical studies. ELT also shows promise as a strategy to forecast target tractability. As an emerging technology, it benefits from incubation at the interface of industry and academia.
引用
收藏
页码:1898 / 1909
页数:12
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