Publications by year

<embed>

Publications by Authors

Recent Publications

More<embed>

Contact Us

Head of Institute: Prof. Oren Tirosh

Administrative manager: Rakefet Kalev

Office Address:
Institute of Biochemistry, Food Science and Nutrition,
Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
Herzl 229, Rehovot 7610001, ISRAEL

Tel: +972 - (0)8-9489385
Fax: +972 - (0)8-9363208
Email Address: rakefetk@savion.huji.ac.il

Design and synthesis of novel protein kinase R (PKR) inhibitors

Citation:

Weintraub, S. ; Yarnitzky, T. ; Kahremany, S. ; Barrera, I. ; Viskind, O. ; Rosenblum, K. ; Niv, M. Y. ; Gruzman, A. Design and synthesis of novel protein kinase R (PKR) inhibitors. 2016, 20, 805 - 819.

Date Published:

2016

Abstract:

Protein kinase RNA-activated (PKR) plays an important role in a broad range of intracellular regulatory mechanisms and in the pathophysiology of many human diseases, including microbial and viral infections, cancer, diabetes and neurodegenerative disorders. Recently, several potent PKR inhibitors have been synthesized. However, the enzyme’s multifunctional character and a multitude of PKR downstream targets have prevented the successful transformation of such inhibitors into effective drugs. Thus, the need for additional PKR inhibitors remains. With the help of computer-aided drug-discovery tools, we designed and synthesized potential PKR inhibitors. Indeed, two compounds were found to inhibit recombinant PKR in pharmacologically relevant concentrations. One compound, 6-amino-3-methyl-2-oxo-N-phenyl-2,3-dihydro-1H-benzo[d]imidazole-1-carboxamide, also showed anti-apoptotic properties. The novel molecules diversify the existing pool of PKR inhibitors and provide a basis for the future development of compounds based on PKR signal transduction mechanism.

Website