5AJV

Human PFKFB3 in complex with an indole inhibitor 1

Summary for 5AJV

• Entry DOI: 10.2210/pdb5ajv/pdb
• Related: 5AJW 5AJX 5AJY 5AJZ 5AK0
• Descriptor: HUMAN PFKFB3, PHOSPHATE ION, (2S)-2-amino-N-[4-[(2-amino-3-cyano-1H-indol-5-yl)oxy]phenyl]-3-hydroxy-propanamide, ... (5 entities in total)
• Functional Keywords: transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 60670.53

Authors

Boyd, S.,Brookfield, J.L.,Critchlow, S.E.,Cumming, I.A.,Curtis, N.J.,Debreczeni, J.E.,Degorce, S.L.,Donald, C.,Evans, N.J.,Groombridge, S.,Hopcroft, P.,Jones, N.P.,Kettle, J.G.,Lamont, S.,Lewis, H.J.,MacFaull, P.,McLoughlin, S.B.,Rigoreau, L.J.M.,Smith, J.M.,St-Gallay, S.,Stock, J.K.,Wheatley, E.R.,Winter, J.,Wingfield, J. (deposition date: 2015-02-27, release date: 2015-04-22, Last modification date: 2024-05-08)

Primary citation

Boyd, S.,Brookfield, J.L.,Critchlow, S.E.,Cumming, I.A.,Curtis, N.J.,Debreczeni, J.,Degorce, S.L.,Donald, C.,Evans, N.J.,Groombridge, S.,Hopcroft, P.,Jones, N.P.,Kettle, J.G.,Lamont, S.,Lewis, H.J.,Macfaull, P.,Mcloughlin, S.B.,Rigoreau, L.J.M.,Smith, J.M.,St-Gallay, S.,Stock, J.K.,Turnbull, A.P.,Wheatley, E.R.,Winter, J.,Wingfield, J.
Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase Pfkfb3.
J.Med.Chem., 58:3611-, 2015

PubMed 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.

PubMed: 25849762
DOI: 10.1021/ACS.JMEDCHEM.5B00352

Experimental method

X-RAY DIFFRACTION (3.01 Å)