For pediatric indications requiring juvenile toxicity testing, the rat is the preferred species. However, for some drugs it might not be an appropriate model or regulatory agencies may also request a non-rodent species. Due to the relatively recent use of Göttingen minipigs, little background data are available.
View Article and Find Full Text PDFBI 882370 is a highly potent and selective RAF inhibitor that binds to the DFG-out (inactive) conformation of the BRAF kinase. The compound inhibited proliferation of human BRAF-mutant melanoma cells with 100× higher potency (1-10 nmol/L) than vemurafenib, whereas wild-type cells were not affected at 1,000 nmol/L. BI 882370 administered orally was efficacious in multiple mouse models of BRAF-mutant melanomas and colorectal carcinomas, and at 25 mg/kg twice daily showed superior efficacy compared with vemurafenib, dabrafenib, or trametinib (dosed to provide exposures reached in patients).
View Article and Find Full Text PDFToxicol Pathol
January 2005
In this report we describe 2 cases of adreno-hepatic fusion (AHF) in Cynomolgus monkeys (Macaca fascicularis) used in short-term toxicity studies. AHF is defined as the union of hepatic tissue with the adrenal gland with close intermingling of the respective parenchymal cells. In this condition, a continuous intervening connective tissue septum is lacking.
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