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

Content Provider	Springer Nature Link
Author	Weintraub, Sagiv Yarnitzky, Tali Kahremany, Shirin Barrera, Iliana Viskind, Olga Rosenblum, Kobi Niv, Masha Y. Gruzman, Arie
Copyright Year	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.
Starting Page	805
Ending Page	819
Page Count	15
File Format	PDF
ISSN	13811991
Journal	Molecular Diversity
Volume Number	20
Issue Number	4
e-ISSN	1573501X
Language	English
Publisher	Springer International Publishing
Publisher Date	2016-08-01
Publisher Place	Cham
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	PKR inhibitors C16 Benzoimidazole derivatives Computer modelling Biochemistry Organic Chemistry Polymer Sciences Pharmacy
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Medicine Drug Discovery Molecular Biology Physical and Theoretical Chemistry Information Systems Catalysis Inorganic Chemistry

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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