8EQ9

Co-crystal structure of PERK with compound 11

This is a non-PDB format compatible entry.

Summary for 8EQ9

• Entry DOI: 10.2210/pdb8eq9/pdb
• Descriptor: Eukaryotic translation initiation factor 2-alpha kinase 3, (2R)-N-[(4M)-4-(4-amino-7-methyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-3-methylphenyl]-2-(3-fluorophenyl)-2-hydroxyacetamide (3 entities in total)
• Functional Keywords: kinase, perk, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 37221.79

Authors

Zhu, G.,Surman, M.D.,Mulvihill, M.J. (deposition date: 2022-10-07, release date: 2022-11-30, Last modification date: 2023-10-25)

Primary citation

Stokes, M.E.,Surman, M.D.,Calvo, V.,Surguladze, D.,Li, A.H.,Gasparek, J.,Betzenhauser, M.,Zhu, G.,Du, H.,Rigby, A.C.,Mulvihill, M.J.
Optimization of a Novel Mandelamide-Derived Pyrrolopyrimidine Series of PERK Inhibitors.
Pharmaceutics, 14:-, 2022

PubMed Abstract: The protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is one of three endoplasmic reticulum (ER) transmembrane sensors of the unfolded protein response (UPR) responsible for regulating protein synthesis and alleviating ER stress. PERK has been implicated in tumorigenesis, cancer cell survival as well metabolic diseases such as diabetes. The structure-based design and optimization of a novel mandelamide-derived pyrrolopyrimidine series of PERK inhibitors as described herein, resulted in the identification of compound , a potent, selective, and orally bioavailable compound suitable for interrogating PERK pathway biology in vitro and in vivo, with pharmacokinetics suitable for once-a-day oral dosing in mice.

PubMed: 36297668
DOI: 10.3390/pharmaceutics14102233

Experimental method

X-RAY DIFFRACTION (2.86 Å)