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Journal Article
Review
Protein kinase R(PKR)-like endoplasmic reticulum kinase (PERK) inhibitors: a patent review (2010-2015).
Expert Opinion on Therapeutic Patents 2017 January
INTRODUCTION: PKR-like endoplasmic reticulum kinase (PERK) is an essential component of the unfolded protein response (UPR) and a critical regulator of protein synthesis during endoplasmic reticulum (ER) stress. Transient PERK activation is protective; however, chronic ER stress and sustained PERK activation can be detrimental to cell health. Many diseases are associated with PERK over-activation, suggestive that small molecule PERK inhibitors may provide new opportunities for treating cancer and neurodegenerative diseases, among others. Areas covered: This review covers the therapeutic potential of PERK modulation and will focus more specifically on small molecule inhibitors of PERK disclosed in the patent literature from 2010-2015. During this time period the first PERK inhibitor patents appeared disclosing novel, potent, and selective inhibitors of PERK. Expert opinion: Compelling preclinical and clinical evidence supports the potential use of PERK modulators for a variety of diseases, particularly cancer and neurodegenerative disease. Potent and selective PERK inhibitors have been characterized pharmacologically and are available for further study. Despite high therapeutic potential, the future clinical use of PERK inhibitors will require thorough safety and toxicity evaluation to gauge therapeutic index and develop a framework for risk-benefit assessment.
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