Drugs in R & D 

About: Drugs in R & D is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Medicine & Pharmacokinetics. It has an ISSN identifier of 1174-5886. It is also open access. Over the lifetime, 655 publications have been published receiving 14046 citations. The journal is also known as: Drugs in research and development & Drugs in research & development.

Auranofin: Repurposing an Old Drug for a Golden New Age

Abstract: Drug discovery, development and registration is an expensive and time-consuming process associated with a high failure rate [Pessetto et al. (Mol Cancer Ther 12:1299–1309, 2013), Woodcock and Woosley (Annu Rev Med 59:1–12, 2008)]. Drug ‘repurposing’ is the identification of new therapeutic purposes for already approved drugs and is more affordable and achievable than novel drug discovery [Pessetto et al. (Mol Cancer Ther 12:1299–1309, 2013)]. Auranofin is a drug that is approved for the treatment of rheumatoid arthritis but is being investigated for potential therapeutic application in a number of other diseases including cancer, neurodegenerative disorders, HIV/AIDS, parasitic infections and bacterial infections [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029–2035, 2013)]. The main mechanism of action of auranofin is through the inhibition of reduction/oxidation (redox) enzymes that are essential for maintaining intracellular levels of reactive oxygen species. Inhibition of these enzymes leads to cellular oxidative stress and intrinsic apoptosis [Pessetto et al. (Mol Cancer Ther 12:1299–1309, 2013), Fan et al. (Cell Death Dis 5:e1191, 2014), Fiskus et al. (Cancer Res 74:2520–2532, 2014), Marzano et al. (Free Radic Biol Med 42:872–881, 2007)]. Drugs such as auranofin that have already been approved for human use [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029–2035, 2013)] can be brought into clinical use for other diseases relatively quickly and for a fraction of the cost of new drugs.

Immunosuppressive and Anti-Inflammatory Mechanisms of Triptolide, the Principal Active Diterpenoid from the Chinese Medicinal Herb Tripterygium wilfordii Hook. f.

Abstract: Extracts of Tripterygium wilfordii hook. f. (leigong teng, Thundergod vine) are effective in traditional Chinese medicine for treatment of immune inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. Characterisation of the terpenoids present in extracts of Tripterygium identified triptolide, a diterpenoid triepoxide, as responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects observed in vitro. Triptolide inhibits lymphocyte activation and T-cell expression of interleukin-2 at the level of transcription. In all cell types examined, triptolide inhibits nuclear factor-κB transcriptional activation at a unique step in the nucleus after binding to DNA. Further characterisation of the molecular mechanisms of triptolide action will serve to elucidate pathways of immune system regulation.

Clinical and Experimental Applications of Sodium Phenylbutyrate

Abstract: Histone acetyltransferase and histone deacetylase are enzymes responsible for histone acetylation and deacetylation, respectively, in which the histones are acetylated and deacetylated on lysine residues in the N-terminal tail and on the surface of the nucleosome core. These processes are considered the most important epigenetic mechanisms for remodeling the chromatin structure and controlling the gene expression. Histone acetylation is associated with gene activation. Sodium phenylbutyrate is a histone deacetylase inhibitor that has been approved for treatement of urea cycle disorders and is under investigation in cancer, hemoglobinopathies, motor neuron diseases, and cystic fibrosis clinical trials. Due to its characteristics, not only of histone deacetylase inhibitor, but also of ammonia sink and chemical chaperone, the interest towards this molecule is growing worldwide. This review aims to update the current literature, involving the use of sodium phenylbutyrate in experimental studies and clinical trials.

Applications of metabolomics in drug discovery and development.

Abstract: Metabolomics is a relatively new field of 'omics' technology that is primarily concerned with the global or system-wide characterization of small molecule metabolites using technologies such as nuclear magnetic resonance, liquid chromatography and/or mass spectrometry. Its unique focus on small molecules and the physiological effects of small molecules aligns the field of metabolomics very closely with the aims and interests of many researchers in the pharmaceutical industry. Because of its conceptual and technical overlap with many aspects of pharmaceutical research, metabolomics is now finding applications that span almost the full length of the drug discovery and development pipeline, from lead compound discovery to post-approval drug surveillance. This review explores some of the most interesting or significant applications of metabolomics as they relate to pharmaceutical research and development. Specific examples are given that show how metabolomics can be used to facilitate lead compound discovery, to improve biomarker identification (for monitoring disease status and drug efficacy) and to monitor drug metabolism and toxicity. Other applications are also discussed, including the use of metabolomics to facilitate clinical trial testing and to improve post-approval drug monitoring. These examples show that metabolomics potentially offer drug researchers and drug regulators an effective, inexpensive route to addressing many of the riskier or more expensive issues associated with the discovery, development and monitoring of drug products.

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.

Abstract: Background Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist.