4X7L

Co-crystal Structure of PERK bound to 4-{2-amino-4-methyl-3-[2-(methylamino)-1,3-benzothiazol-6-yl]benzoyl}-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one inhibitor

Summary for 4X7L

• Entry DOI: 10.2210/pdb4x7l/pdb
• Related: 4X7H 4X7J 4X7K 4X7N 4X7P
• Descriptor: Eukaryotic translation initiation factor 2-alpha kinase 3,Eukaryotic translation initiation factor 2-alpha kinase 3, 4-{2-amino-4-methyl-3-[2-(methylamino)-1,3-benzothiazol-6-yl]benzoyl}-1-methyl-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one, L(+)-TARTARIC ACID, ... (5 entities in total)
• Functional Keywords: catalytic domain, transferase-transferase inhibitor, complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein: Q9NZJ5
• Total number of polymer chains: 1
• Total formula weight: 37604.20

Authors

Shaffer, P.L.,Long, A.M.,Chen, H. (deposition date: 2014-12-09, release date: 2015-01-28, Last modification date: 2024-02-28)

Primary citation

Smith, A.L.,Andrews, K.L.,Beckmann, H.,Bellon, S.F.,Beltran, P.J.,Booker, S.,Chen, H.,Chung, Y.A.,D'Angelo, N.D.,Dao, J.,Dellamaggiore, K.R.,Jaeckel, P.,Kendall, R.,Labitzke, K.,Long, A.M.,Materna-Reichelt, S.,Mitchell, P.,Norman, M.H.,Powers, D.,Rose, M.,Shaffer, P.L.,Wu, M.M.,Lipford, J.R.
Discovery of 1H-Pyrazol-3(2H)-ones as Potent and Selective Inhibitors of Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK).
J.Med.Chem., 58:1426-1441, 2015

PubMed Abstract: The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.

PubMed: 25587754
DOI: 10.1021/jm5017494

Experimental method

X-RAY DIFFRACTION (1.9 Å)