1133754-22-9Relevant academic research and scientific papers
Generating Selective Leads for Mer Kinase Inhibitors-Example of a Comprehensive Lead-Generation Strategy
Nissink, J. Willem M.,Bazzaz, Sana,Blackett, Carolyn,Clark, Matthew A.,Collingwood, Olga,Disch, Jeremy S.,Gikunju, Diana,Goldberg, Kristin,Guilinger, John P.,Hardaker, Elizabeth,Hennessy, Edward J.,Jetson, Rachael,Keefe, Anthony D.,McCoull, William,McMurray, Lindsay,Olszewski, Allison,Overman, Ross,Pflug, Alexander,Preston, Marian,Rawlins, Philip B.,Rivers, Emma,Schimpl, Marianne,Smith, Paul,Truman, Caroline,Underwood, Elizabeth,Warwicker, Juli,Winter-Holt, Jon,Woodcock, Simon,Zhang, Ying
, p. 3165 - 3184 (2021/04/06)
Mer is a member of the TAM (Tyro3, Axl, Mer) kinase family that has been associated with cancer progression, metastasis, and drug resistance. Their essential function in immune homeostasis has prompted an interest in their role as modulators of antitumor immune response in the tumor microenvironment. Here we illustrate the outcomes of an extensive lead-generation campaign for identification of Mer inhibitors, focusing on the results from concurrent, orthogonal high-throughput screening approaches. Data mining, HT (high-throughput), and DECL (DNA-encoded chemical library) screens offered means to evaluate large numbers of compounds. We discuss campaign strategy and screening outcomes, and exemplify series resulting from prioritization of hits that were identified. Concurrent execution of HT and DECL screening successfully yielded a large number of potent, selective, and novel starting points, covering a range of selectivity profiles across the TAM family members and modes of kinase binding, and offered excellent start points for lead development.
DERIVATIVES OF ADENINE AND 8-AZA-ADENINE AND USES THEREOF-796
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Page/Page column 94; 99-100, (2009/04/25)
The invention relates to chemical compounds, or pharmaceutically acceptable salts thereof of the formula (I): which have bacterial MurI inhibitory activity and are accordingly useful for their treatment and prophylaxis of bacterial infection, e.g., E.faecalis or E. faeciuminfection. Further, the invention relates to methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of the compounds, to pharmaceutical compositions containing them, and to their use in the manufacture of medicaments of use in the treatment and prevention of various bacterial diseases in a warm-blooded animalsuch as man.
