3ODK

Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution

Summary for 3ODK

• Entry DOI: 10.2210/pdb3odk/pdb
• Related: 3KAB 3KAC 3KAD 3KAF 3KAG 3KAH 3KAI 3KCE
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, 2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL, 3-pyridin-2-yl-1H-pyrazole-5-carboxylic acid, ... (4 entities in total)
• Functional Keywords: sbdd, ppiase, isomerase, rotamase, small molecule, proline directed kinase, cell cycle, oncogenic transformation, nucleus, phosphoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q13526
• Total number of polymer chains: 1
• Total formula weight: 19068.13

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: 2010-08-11, release date: 2010-10-27, Last modification date: 2024-02-21)

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., 20:6483-6488, 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 (2.3 Å)