Drug discovery today
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Drug discovery today · Jul 2012
Orphan drug development: an economically viable strategy for biopharma R&D.
Orphan drug incentives have stimulated research into diseases with significant unmet medical need. Although the targeting of orphan diseases is seen by industry as an attractive strategy, there are limited economic data available to support its use. ⋯ Moreover, we suggest that orphan drugs have greater profitability when considered in the full context of developmental drivers including government financial incentives, smaller clinical trial sizes, shorter clinical trial times and higher rates of regulatory success. The data support the targeting of rare diseases as an important component of a successful biopharma R&D strategy.
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The presence of sufficient skeletal muscle mass is of paramount importance for body function and the myostatin cascade is known to inhibit muscle growth in mammals. In addition, myostatin seems to have an important role in the cross-talk between skeletal muscle and adipose tissue and is involved in insulin sensitivity. In this article we highlight the latest developments related to the myostatin system, emphasizing therapeutic implications for wasting diseases and also the involvement of the system in other organs, in addition to skeletal muscle, such as heart or adipose tissue. Moreover, we highlight the possible role of the myostatin system in the cross-talk between skeletal muscle and adipose tissue, an important aspect that deserves consideration in wasting diseases.
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Drug discovery today · Jun 2012
ReviewTargeting neuronal adenylyl cyclase for the treatment of chronic pain.
Pain research is currently undergoing dramatic changes. In the area of basic pain research, new discoveries have been made towards the understanding of pain transmission, modulation and plasticity. ⋯ In this review, I focus on activity-dependent potentiation in pain-related cortical areas and recent translational research on adenylyl cyclase subtype 1 (AC1) as a novel target for treating chronic pain. In particular, I discuss the AC1 inhibitor, NB001, which produces powerful analgesic effects in animal models of chronic pain by inhibiting chronic pain-related cortical potentiation.
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Drug discovery today · May 2012
Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival.
In an effort to uncover systematic learnings that can be applied to improve compound survival, an analysis was performed on data from Phase II decisions for 44 programs at Pfizer. It was found that not only were the majority of failures caused by lack of efficacy but also that, in a large number of cases (43%), it was not possible to conclude whether the mechanism had been tested adequately. A key finding was that an integrated understanding of the fundamental pharmacokinetic/pharmacodynamic principles of exposure at the site of action, target binding and expression of functional pharmacological activity (termed together as the 'three Pillars of survival') all determine the likelihood of candidate survival in Phase II trials and improve the chance of progression to Phase III.