Gentronix was founded in 1999 by Richard Walmsley, Ph.D., with a yeast cell-based genotoxicity assay as the original technology. Today, the company seeks to minimize late preclinical failure by eliminating unsatisfactory candidates before they advance to these later stages of evaluation.
According to Dr. Walmsley, the ICH guidelines mandate that regulatory genotoxicity assessment be performed before the candidate enters into clinical trials. Positive genotoxicity data can lead to costly delays in clinical trials while further in vitro and in vivo studies are carried out to make a full risk assessment. That is why screening much earlier than preclinical safety assessment is a good idea.
To meet these challenges, the company has developed the mammalian cell GreenScreen HC platform, named after its use of the green fluorescent protein reporter. The reporter responds to the GADD45a gene, which mediates the adaptive response to genotoxic stress. Its complex regulatory elements respond to all classes of genotoxins including direct-acting mutagens, clastogens, and aneugens resulting in a fluorescence reaction in responsive cells.
The procedure is extremely rapid—yielding results over a two-day period—and has been validated in a number of studies published in peer-reviewed journals. The goal is to help narrow large numbers of potential compounds down to the handful that will be viable drug candidates. An important feature of the platform is its ability to detect promutagens and procarcinogens—compounds that must be converted by liver enzymes to an active form from their initial inactive state.