Drug, drugs bottlenecks

Walker, M. J. A., Barrett, T., and Guppy, L.J. (2004). Functional pharmacology The drug discovery bottleneck Drug Disc. Today 3 208-215. 

Fig. 3 Stepwise development of antiviral resistance. Because of the rapid mutation rate of viruses, the virus population before treatment (a) contains variants, which display by chance a low level of resistance to the drug (indicated by the darker hue). Treatment with suboptimal levels of an antiviral drug (b) creates a bottleneck, which selects for these variants (c). These can further replicate in the presence of the drug and thereby acquire additional mutations, leading to resistant variants with enhanced replicative fitness (d)...

More recently, the bottleneck of drug research has shifted from hit-and-lead discovery to lead optimization, and more specifically to PK lead optimization. Some major reasons are (i) the imperative to reduce as much as feasible the extremely costly rate of attrition prevailing in preclinical and clinical phases, and (ii) more stringent concerns for safety. The testing of ADME properties is now done much earlier, i.e. before a decision is taken to evaluate a compound in the clinic. 

Generally, the stratum corneum is considered to be the rate limiting layer of the skin with regard to transdermal drug absorption. However, for the invasion of very lipophilic compounds, the bottleneck moves from the stratum corneum down to the viable, very hydrophilic layer of the epidermis, due to substances reduced solubility in this rather aqueous layer [14],... 

An often-noted paradox in HTS is that as microplate wells and assay volumes have become smaller, automated systems to accommodate them have grown ever larger. This truth raises an important point Because HTS is not a bottleneck in the drug-discovery... 

Wess, G. How to escape the bottleneck of medicinal chemistry. Drug Disc. Today 2002, 7, 533-535. 

Identification of the protein target that interacts with a molecule is a bottleneck in drug discovery. Here we will deal with one branch of this important venture. 

Giuliano KA, DeBiasio RL, Dunlay RT et al (1997) High-content screening a new approach to easing key bottlenecks in the drug discovery process. J Biomol Screen 2 249... 

NDA) approvals. Since 1991, the FDA has persistently approved 70-80% of all NDAs submitted. Although the quality bar at the FDA has clearly been raised as clinical standards of care have improved, FDA is certainly not as much of a bottleneck as critics claim. The reason is that prior to deciding on an NDA submission, the pharma industry itself looks very carefully at the approvability of a developmental drug. 

Borman, S. (2006) Improving efficiency. To eliminate R8cD bottlenecks, drug companies are evaluating all phases of discovery and development and are using novel approaches to speed them up. Chem Eng News 84, 56-78. 

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