Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- GlaxoSmithKline, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426, USA.
- GlaxoSmithKline, 830 Winter Street, Waltham, Massachusetts 02451, USA.
- Diseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, 28760, Tres Cantos, Madrid, Spain.
- School of Biosciences, University of Birmingham
The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.
|Early online date||17 Jul 2017|
|Publication status||E-pub ahead of print - 17 Jul 2017|