Pre-clinical development

The clinical validation of new approaches to raise functional HDL will potentially lead to a paradigm shift in the treatment of atherosclerosis, dyslipidemia and metabolic syndrome. 

Ansell, G. Datta, D. W. Garber and A. M. Fogelman, Arterioscler. Thromb. Vase. Biol., 2005, 25, 1325. 

Rudolf Giger, Henri Mattes and Hans-Jiirgen Pfannkuche 

Novartis Institutes for Biomedical Research, Novartis Pharma AG, CH-4002 Basel, Switzerland 

Annual Reports in Medicinal Chemistry, Volume 42 ISSN 0065-7743, DOI 10.1016/S0065-7743(07)42013-9 

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All the nucleoside (and nucleotide) analogues that have entered the clinic for the treatment of HBV infections (i.e., nucleoside analogues lamivudine, entecavir, tel-bivudine nucleotide analogues adefovir and tenofovir) are fairly well tolerated without side effects that would preclude their long-term usage. The nucleoside analogues in (pre)clinical development for the treatment of HCV infections are not yet sufficiently advanced to assess their tolerability and/or safety. 

McAusiane, N., Accelerating pre-clinical development by successful integration into drug discovery . 

Case Study 2 Pre-Clinical Development of CDD-0102A for the Treatment of Alzheimer s Disease William S. Messer, Ph.D., Department of Pharmacology, The University of Toledo... 

Purpose The Therapeutics for Rare and Neglected Diseases (TRND) program was established in 2009 to encourage and accelerate the pre-clinical development of therapeutics directed at rare and neglected diseases. These are diseases that are classified as effecting fewer than 20,000 people in the United States at a given time, and are also known as orphan... 

PI3K/AKT Kinase Pathway Inhibitors in Pre-Clinical Development 366... 

PI3K/AKT KINASE PATHWAY INHIBITORS IN PRE-CLINICAL DEVELOPMENT... 

The central role that the PI3K/AKT pathway plays in cancer continues to fuel excitement in this arena as a potential target for cancer therapy. Progress with small molecule AKT inhibitors continues to be made, as judged by the compounds described in this review. However, the full scope of the clinical effectiveness of targeting this pathway has yet to be proven, as most of the reported small molecule AKT inhibitors are still in pre-clinical development, with only a few examples in early phase clinical trials. 

Ledizet M, Harrison LM, Koskia RA, Cappello M. (2005) Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates. CurrMed Chem Cardiovasc Hematol Agents 3 1-10. 

Lobell RB, Kohl NE. Pre-clinical development of famesyltransferase inhibitors. Cancer Metastasis Rev 1998 17 203-210. 

Based on these results, lO-CFs-analogues of dihydroartemisinin (DMA), arte-mether, arteetherand artesunate have been prepared. They also exhibit very interesting in vivo anti-malarial properties, a better stability under stomach acidic conditions. A prolonged plasma half-life was demonstrated for some of them [171,173], This approach has led to the pre-clinical development of the orally active 10-trifluoromethyl DMA and a 10-trifluoromethyl deoxoartemisinin (Fig. 73) [170-172],... 

An optimised (having sufficient potential as a therapeutic candidate to be tested in humans) compound (small molecule) selected to enter pre-clinical development. 

Key words Toxicity testing, pre-clinical development, inbred strain, drug development, factorial experimental designs, statistics, signal/noise ratio. 

Third-generation emulsions are currently in early pre-clinical development (2). The absence of toxicity of these new emulsions has been demonstrated in endothelial cell cultures and in animal organ preservation studies. 

We thank Scott Wilkinson, MS, Steve Jones, PhD, Tom Rollins, and other members of the Sepracor Inc. Clinical and Pre-Clinical Development teams, and Blaise Frederick, PhD, Nick Bolo, PhD and Perry Renshaw, MD, PhD at McLean Hospital Brain Imaging Center in Boston, MA for their scientific contributions to the tecastemizole work. In addition, we are grateful to Sepracor, Inc. for permission to publish the tecastemizole spectra and data. 

US, a decoy ODN targeting NF-kB is currently under pre-clinical development for rheumatoid arthritis and dermatitis (http // wwwl. corgentech.com/cgt/inflammation). 

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