3IKG

Structure-Based Design of Novel PIN1 Inhibitors (I)

Summary for 3IKG

• Entry DOI: 10.2210/pdb3ikg/pdb
• Related: 3I6C 3IK8 3IKD
• Descriptor: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, (2R)-2-[(1-benzothiophen-2-ylcarbonyl)amino]-3-(3-methylphenyl)propyl phosphate (3 entities in total)
• Functional Keywords: sbdd, ppiase, cell cycle, isomerase, small molecule, nucleus, phosphoprotein, rotamase, peptidyl-prolyl cis-trans isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q13526
• Total number of polymer chains: 2
• Total formula weight: 28131.17

Authors

Parge, H.,Ferre, R.A.,Greasley, S.,Matthews, D. (deposition date: 2009-08-05, release date: 2009-09-22, Last modification date: 2023-09-06)

Primary citation

Guo, C.,Hou, X.,Dong, L.,Dagostino, E.,Greasley, S.,Ferre, R.,Marakovits, J.,Johnson, M.C.,Matthews, D.,Mroczkowski, B.,Parge, H.,Vanarsdale, T.,Popoff, I.,Piraino, J.,Margosiak, S.,Thomson, J.,Los, G.,Murray, B.W.
Structure-based design of novel human Pin1 inhibitors (I).
Bioorg.Med.Chem.Lett., 19:5613-5616, 2009

PubMed Abstract: Pin1 is a member of the cis-trans peptidyl-prolyl isomerase family with potential anti-cancer therapeutic value. Here we report structure-based de novo design and optimization of novel Pin1 inhibitors. Without a viable lead from internal screenings, we designed a series of novel Pin1 inhibitors by interrogating and exploring a protein crystal structure of Pin1. The ligand efficiency of the initial concept molecule was optimized with integrated SBDD and parallel chemistry approaches, resulting in a more attractive lead series.

PubMed: 19729306
DOI: 10.1016/j.bmcl.2009.08.034

Experimental method

X-RAY DIFFRACTION (1.86 Å)