2XP4

DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION

Summary for 2XP4

• Entry DOI: 10.2210/pdb2xp4/pdb
• Related: 1F8A 1I6C 1I8G 1I8H 1NMV 1NMW 1PIN 1ZCN 2F21 2XP3 2XP5 2XP6 2XP7 2XP8 2XP9 2XPA 2XPB
• Descriptor: PEPTIDYL-PROLYL CIS-TRANS ISOMERASE NIMA-INTERACTING 1, DODECAETHYLENE GLYCOL, 2-phenyl-1H-imidazole-4-carboxylic acid, ... (4 entities in total)
• Functional Keywords: isomerase, proline directed kinase, cell cycle, oncogenic transformation
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 19259.35

Authors

Potter, A.,Oldfield, V.,Nunns, C.,Fromont, C.,Ray, S.,Northfield, C.J.,Bryant, C.J.,Scrace, S.F.,Robinson, D.,Matossova, N.,Baker, L.,Dokurno, P.,Surgenor, A.E.,Davis, B.E.,Richardson, C.M.,Murray, J.B.,Moore, J.D. (deposition date: 2010-08-25, release date: 2011-01-12, Last modification date: 2023-12-20)

Primary citation

Potter, A.,Oldfield, V.,Nunns, C.,Fromont, C.,Ray, S.,Northfield, C.J.,Bryant, C.J.,Scrace, S.F.,Robinson, D.,Matossova, N.,Baker, L.,Dokurno, P.,Surgenor, A.E.,Davis, B.,Richardson, C.M.,Murray, J.B.,Moore, J.D.
Discovery of Cell-Active Phenyl-Imidazole Pin1 Inhibitors by Structure-Guided Fragment Evolution.
Bioorg.Med.Chem.Lett., 20:6483-, 2010

PubMed Abstract: Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.

PubMed: 20932746
DOI: 10.1016/J.BMCL.2010.09.063

Experimental method

X-RAY DIFFRACTION (1.8 Å)