3I6C

Structure-Based Design of Novel PIN1 Inhibitors (II)

Summary for 3I6C

• Entry DOI: 10.2210/pdb3i6c/pdb
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, 3-fluoro-N-(naphthalen-2-ylcarbonyl)-D-phenylalanine (3 entities in total)
• Functional Keywords: sbdd, small molecule, ppiase, cell cycle, isomerase, nucleus, phosphoprotein, rotamase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q13526
• Total number of polymer chains: 2
• Total formula weight: 28336.43

Authors

Greasley, S.E.,Ferre, R.A. (deposition date: 2009-07-06, release date: 2010-04-21, Last modification date: 2024-02-21)

Primary citation

Dong, L.,Marakovits, J.,Hou, X.,Guo, C.,Greasley, S.,Dagostino, E.,Ferre, R.,Johnson, M.C.,Kraynov, E.,Thomson, J.,Pathak, V.,Murray, B.W.
Structure-based design of novel human Pin1 inhibitors (II).
Bioorg.Med.Chem.Lett., 20:2210-2214, 2010

PubMed Abstract: Following the discovery of a novel series of phosphate-containing small molecular Pin1 inhibitors, the drug design strategy shifted to replacement of the phosphate group with an isostere with potential better pharmaceutical properties. The initial loss in potency of carboxylate analogs was likely due to weaker charge-charge interactions in the putative phosphate binding pocket and was subsequently recovered by structure-based optimization of ligand-protein interactions in the proline binding site, leading to the discovery of a sub-micromolar non-phosphate small molecular Pin1 inhibitor.

PubMed: 20207139
DOI: 10.1016/j.bmcl.2010.02.033

Experimental method

X-RAY DIFFRACTION (1.3 Å)