This web page was produced as an assignment for Genetics 564, an undergraduate course at UW-Madison
What is a small molecule screen?
Chemical genetics involves the use of small, inorganic compounds to perturb biological systems, both in an effort to better understand the systems and to identify potential therapeutic agents. It is often not immediately clear, however, the impact a small molecule will have on its target system. For this reason, screens are often performed to systematically examine the effects of small molecule libraries on a protein or process of interest [1].
What compounds have been found in PKD1 chemical genetic screens?
Small molecule screens have suggested that CFTR inhibitors slow growth in polycystic kidney disease. The CFTR protein (cystic fibrosis transmembrane conductance regulator) is important for chloride transport. The compounds that have been shown to reduce cyst growth in polycystic kidney disease models are tetrazolo-CFTR(inh)-172 and Ph-GlyH-101 [2].
Analysis
The inhibition of cyst growth by these compounds generally makes sense, given that fluid accumulation occurs upon cyst growth in patients with polycystic kidney disease and that the CFTR protein has been implicated in epithelial chloride secretion leading to cyst growth. The identification of these molecules is thus an interesting avenue for further research in the search for effective polycystic kidney disease therapeutics. Although interesting, however, identification of these compounds does not yet constitute treatment.
References
[1] Stockwell, B. (2004). Exploring biology with small organic molecules. Nature 432: 846-854. [2] [banner image] Yang, B., Sonawane, N., Zhao, D. Somlo, S., Verkman, A.S. (2008). Small molecule CFTR inhibitors slow cyst growth in polycystic kidney disease. Journal of the American Society of Nephrology. 19:1300-1310. doi: 10.1681/ASN.2007070828 |
Site created by: Elizabeth Roeske
Last updated: 5.12.2014 University of Wisconsin-Madison: Genetics 564 |