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Can the pharmaceutical industry reduce attrition rates
Ismail Kola,John Landis +1 more
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TLDR
The pharmaceutical industry faces considerable challenges, both politically and fiscally, and the fiscal pressures that face the industry from the perspective of R&D are dealt with.Abstract:
The pharmaceutical industry faces considerable challenges, both politically and fiscally. Politically, governments around the world are trying to contain costs and, as health care budgets constitute a very significant part of governmental spending, these costs are the subject of intense scrutiny. In the United States, drug costs are also the subject of intense political discourse. This article deals with the fiscal pressures that face the industry from the perspective of R&D. What impinges on productivity? How can we improve current reduced R&D productivity?read more
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Principles of nanoparticle design for overcoming biological barriers to drug delivery
TL;DR: By successively addressing each of the biological barriers that a particle encounters upon intravenous administration, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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Network pharmacology: the next paradigm in drug discovery.
TL;DR: A new appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development--efficacy and toxicity.
Journal ArticleDOI
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Steven M. Paul,Daniel S. Mytelka,Dunwiddie Christopher T,Charles C. Persinger,Bernard H. Munos,Stacy R. Lindborg,Aaron Leigh Schacht +6 more
TL;DR: A detailed analysis based on comprehensive, recent, industry-wide data is presented to identify the relative contributions of each of the steps in the drug discovery and development process to overall R&D productivity and propose specific strategies that could have the most substantial impact in improving R &D productivity.
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The influence of drug-like concepts on decision-making in medicinal chemistry
TL;DR: Analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development.
Journal ArticleDOI
pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures
TL;DR: A novel approach (pkCSM) which uses graph-based signatures to develop predictive models of central ADMET properties for drug development and performs as well or better than current methods.
References
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Journal ArticleDOI
The price of innovation: new estimates of drug development costs
TL;DR: The research and development costs of 68 randomly selected new drugs were obtained from a survey of 10 pharmaceutical firms and used to estimate the average pre-tax cost of new drug development.
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BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.
Steven L. Roberds,John P. Anderson,Guriqbal Basi,Michael Jerome Bienkowski,Daniel G. Branstetter,Karen S. Chen,Stephen B. Freedman,Normand Frigon,Dora Kate Games,Kang Hu,Kelly Johnson-Wood,Karl Kappenman,Thomas T. Kawabe,Ismail Kola,Ralf Kuehn,Mike Lee,Weiqun Liu,Ruth Motter,Nanette F. Nichols,Michael Power,David W. Robertson,Dale Schenk,Michael Schoor,George Shopp,Mary E. Shuck,Sukanto Sinha,Kjell A. Svensson,Gwen Tatsuno,Hartmut Tintrup,John A. Wijsman,Sarah Wright,Lisa McConlogue +31 more
TL;DR: The findings that BACE is the primary beta- secretase activity in brain and that loss of beta-secretase activity produces no profound phenotypic defects with a concomitant reduction in beta-amyloid peptide clearly indicate that Bace is an excellent therapeutic target for treatment of AD.
Journal ArticleDOI
Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization.
Maxine Gowen,Francesca Lazner,R.A. Dodds,Rasesh Kapadia,John A. Feild,Michael Tavaria,Ivan Bertoncello,F. Drake,Silva Zavarselk,Irene Tellis,Paul J. Hertzog,Christine Debouck,Ismail Kola +12 more
TL;DR: Close histologic examination of bone histology revealed fully differentiated osteoclasts apposed to small regions of demineralized bone, which strongly suggests that cathepsin K–deficient osteoclast are capable ofdemineralizing the extracellular matrix but are unable to adequately remove the deminERALized bone.
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Drug discovery--an operating model for a new era.
Scott D. Myers,Ann Baker +1 more
TL;DR: Despite the advent of new science and technologies, drug developers will need to make radical changes in their operations if they are to remain competitive and innovative.