Drug discovery today
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Drug discovery today · May 2014
ReviewToward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines.
Recycling old drugs, rescuing shelved drugs and extending patents' lives make drug repositioning an attractive form of drug discovery. Drug repositioning accounts for approximately 30% of the newly US Food and Drug Administration (FDA)-approved drugs and vaccines in recent years. ⋯ It requires a comprehensive understanding of the available methods gained by evaluating both biological and pharmaceutical knowledge and the elucidated mechanism-of-action of drugs. Here, we provide guidance for prioritizing and integrating drug-repositioning methods for specific drug-repositioning pipelines.
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Drug discovery today · May 2014
ReviewSmall molecule inhibitors of histone acetyltransferases and deacetylases are potential drugs for inflammatory diseases.
Lysine acetylation is a reversible post-translational modification (PTM) of cellular proteins and represents an important regulatory switch in signal transduction. Lysine acetylation, in combination with other PTMs, directs the outcomes as well as the activation levels of important signal transduction pathways such as the nuclear factor (NF)-κB pathway. Small molecule modulators of the 'writers' (HATs) and 'erasers' (HDACs) can regulate the NF-κB pathway in a specific manner. This review focuses on the effects of frequently used HAT and HDAC inhibitors on the NF-κB signal transduction pathway and inflammatory responses, and their potential as novel therapeutics.
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Drug discovery today · May 2014
ReviewImmunosuppressive peptides and their therapeutic applications.
The immune system is vital for detecting and evading endogenous and exogenous threats to the body. Failure to regulate this homeostasis leads to autoimmunity, which is often associated with malfunctioning T cell signaling. ⋯ For example, plant cyclotides effectively inhibit T lymphocyte proliferation. They are composed of a head-to-tail cyclized backbone and a cystine-knot motif, which confers them with remarkable stability, thus making them attractive pharmaceutical tools.