Drug discovery today
-
Drug discovery today · Sep 2014
ReviewStrategies for targeting the androgen receptor axis in prostate cancer.
Androgen receptor (AR) signaling plays a critical role in prostate cancer cell proliferation, survival, and differentiation. Therapeutic strategies targeting the androgen receptor have been developed for the treatment of metastatic hormone-naïve prostate cancer; however, despite effective targeting recent studies have demonstrated that during progression to a castrate-resistant phenotype there is restoration of AR target gene expression. On the basis of this observation, second-generation therapeutics have been developed to target AR in the castrate-resistant setting resulting in a survival benefit. In this review we will discuss the mechanisms promoting AR signaling and the development of second-generation therapeutics targeting AR in castrate-resistant prostate cancer.
-
Drug discovery today · Sep 2014
Review Comparative StudyReversal of target-specific oral anticoagulants.
Target-specific oral anticoagulants (TSOACs) provide safe and effective anticoagulation for the prevention and treatment of thrombosis in a variety of clinical settings by interfering with the activity of thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban, edoxaban, betrixaban). Although TSOACs have practical advantages over vitamin K antagonists (VKAs), there are currently no antidotes to reverse their anticoagulant effect. ⋯ We discuss important limitations of existing evidence, which is derived from studies in human volunteers, animal models and in vitro experiments. Studies evaluating the safety and efficacy of reversal agents on clinical outcomes such as bleeding and mortality in patients with TSOAC-associated bleeding are needed.
-
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.
-
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.
-
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.