 |
8, S1, S40–S43 (2007)
doi:10.1038/sj.embor.7400939
Figures and Tables
Thinking inside the box. To cope with an increasing disease burden, drug discovery needs biologically relevant and predictive testing systems
Lars E. Sundstrom
| |
| | |
| |
|
| | |
| | Figures | |
| |
|
|
Figure 1
Comparison of target-based drug discovery with black-box phenotypic screens.
|
|
Figure 2
Black-box systems that can be used for phenotypic screening. There is a trade-off between the biological complexity and relevance of the test systems and the number of compounds that can be tested. At one end of the spectrum, testing could be performed directly in humans; however, this is unlikely to be ethically acceptable as the risks will be too high. Animal models based on mammals are now the most frequently used system, although this is increasingly seen as unethical and sometimes translates poorly to human conditions. Invertebrates have emerged as biological systems that offer many advantages, as drugs can be screened in whole organisms; however, translation to humans still needs to be proven. Computer modelling has recently become popular, but has yet to prove that it can produce new molecules that translate to human efficacy. Simple two-dimensional tissue-culture systems have long been available. Sometimes referred to as high-content systems, they can be generated using primary human and animal cells or immortalized cell lines. The drawback with two-dimensional cell systems is that they do not reflect physiological parameters, and can therefore produce misleading data. More recently, three-dimensional tissues either taken from living mammals or re-engineered in vitro are being developed as the next generation of screening tools. These systems often reflect complexity at the organ level and are referred to as 'organotypic'.
|
|
|
| | |
|
