Drug discovery today
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Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. ⋯ Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.
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Drug discovery today · Dec 2014
ReviewPharmacological treatment of chronic obstructive pulmonary disease: from evidence-based medicine to phenotyping.
Chronic obstructive pulmonary disease (COPD) is characterized by large phenotype variability, reflected by a highly variable response to pharmacological treatment. Nevertheless, current guidelines suggest that patients with COPD of similar severity should be treated in the same way. ⋯ The clinical importance of phenotypes is changing the paradigm of COPD management from evidence-based to personalized medicine. However, the personalized pharmacological strategy of COPD has to be validated in future clinical studies.
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This short review will highlight recent clinical and basic research that supports the therapeutic utility of ketamine as a rapid-acting, life-saving antidepressant and a versatile analgesic. After 50 years of use as a dissociative anesthetic and misuse as a street drug, ketamine has re-emerged as a useful off-label agent for ameliorating various types of pain and resistant depression. In addition to its ability to inhibit N-methyl-D-aspartate (NMDA) receptors, the diverse actions of ketamine might involve epigenetic mechanisms such as microRNA regulation. Thus, ketamine is transitioning from being the pharmacologist's nightmare to one of the most interesting developments in the pharmacology of depression and pain.
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Drug discovery today · Nov 2014
ReviewCrowdfunding drug development: the state of play in oncology and rare diseases.
In this article, we present descriptive data on 125 crowdfunding campaigns aimed at financing research in oncology (including basic research, drug discovery, and clinical trials). We also describe five campaigns that have succeeded in raising substantial funds to support the development of treatments for ultrarare diseases. The data suggest that crowdfunding is a viable approach to supporting early proof-of-concept research that could allow researchers in oncology and rare diseases to succeed in traditional grant competitions or to attract private investment. The data also suggest that such an approach could become a valuable additional source of funding for early-stage innovators in the drug development arena.
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Drug discovery today · Oct 2014
ReviewHarnessing the anti-inflammatory potential of palmitoylethanolamide.
Palmitoylethanolamide (PEA) is a peroxisome proliferator-activated receptor alpha (PPAR-α) ligand that exerts anti-inflammatory, analgesic and neuroprotective actions. PEA is synthetized from phospholipids through the sequential actions of N-acyltransferase and N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD), and its actions are terminated by its hydrolysis by two enzymes, fatty acid amide hydrolase (FAAH) and N-acylethanolamine-hydrolysing acid amidase (NAAA). ⋯ Recent studies with NAAA inhibitors put forth this enzyme as capable of increasing PEA levels in vivo in inflammatory processes, and identified it as an interesting target for drug discovery research. Thus, PEA hydrolysis inhibitors could constitute potential therapeutic alternatives in chronic inflammatory and neurodegenerative diseases.