| Literature DB >> 25849762 |
Scott Boyd1, Joanna L Brookfield2, Susan E Critchlow1, Iain A Cumming2, Nicola J Curtis1, Judit Debreczeni1, Sébastien L Degorce1, Craig Donald1, Nicola J Evans3, Sam Groombridge1, Philip Hopcroft1, Neil P Jones3, Jason G Kettle1, Scott Lamont1, Hilary J Lewis1, Philip MacFaull1, Sheila B McLoughlin2, Laurent J M Rigoreau2, James M Smith2, Steve St-Gallay1, Julie K Stock3, Andrew P Turnbull3, Edward R Wheatley3, Jon Winter1, Jonathan Wingfield1.
Abstract
A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.Entities:
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Year: 2015 PMID： 25849762 DOI： 10.1021/acs.jmedchem.5b00352
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446