Detail of "196612-93-8"

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Caenorhabditis elegans as model system for rapid toxicity assessment of pharmaceutical compounds

Caenorhabditis elegans as model system for rapid toxicity assessment of pharmaceutical compounds. Dengg, Marlene; van Meel, Jacques C. A. (Boehringer Ingelheim Austria GmbH, Vienna 1121, Austria). Journal of Pharmacological and Toxicological Methods, 50(3), 209-214 (English) 2004 Elsevier B.V. CODEN: JPTMEZ. ISSN: 1056-8719. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The model organism Caenorhabditis elegans is widely used for genetic studies as well as a living biomonitor in ecotoxicol. In this study, the authors investigated whether C. elegans may represent a suitable model for rapid preliminary toxicity studies of pharmaceutical compds. For this purpose, the authors used the EGFR kinase inhibitors BIBU1361, BIBX1382, and an inactive chem. analog BIBU1476. As a first parameter to score for toxicity, the authors detd. lethality of the wild-type C. elegans strain N2 (Bristol) in the presence of the compds. The transgenic C. elegans strain PC72 (lacZ, heat shock protein-16 [hsp-16] construct) was used as a report organism for toxic effects. PC72 expresses b-Galactosidase which is induced by hsp-16 in direct response when exposed to toxic compds. The expression of b-Galactosidase in cells was subsequently visualized by histochem. staining with X-Gal. A rank order of potency with respect to lethality was established: BIBU1361>BIBX1382>>BIB1476. The induction of b-Galactosidase was concn.-dependent for each compd. and demonstrated the same order of potency as obsd. for lethality. Furthermore, these compds. showed the same order for lethality in rodents, the first requirement of validation. These results indicate that wild-type C. elegans and the transgenic strain PC72 are both suitable models to det. the toxicity of pharmaceutical compds. This approach allows for an easy and fast ranking of compd.Except for chemicals metioned above, 196612-93-8 is also used. toxicity, which may lead to a more rational choice for further in vivo tests. .