Journal of Clinical Toxicology
Open Access
ISSN: 2161-0495
ISSN: 2161-0495
Kelly M Credille
Tanzania
Research Article
Nonclinical Safety Evaluation of a Transforming Growth Factor β Receptor I Kinase Inhibitor in Fischer 344 Rats and Beagle Dogs
Author(s): Anja J Stauber, Kelly M Credille, Lewis L Truex, William J Ehlhardt and Jamie K YoungAnja J Stauber, Kelly M Credille, Lewis L Truex, William J Ehlhardt and Jamie K Young
Abstract
Objective: The transforming growth factor β (TGF-β) pathway regulates diverse cellular functions and plays a prominent role in diseases such as cancer, autoimmune disorders and cardiovascular disease. LY2157299 monohydrate (LY2157299) is a potent and selective inhibitor of TGF-β receptor I kinase that is under clinical evaluation for the treatment of advanced cancer.
Methods: This paper characterizes the toxicity profile of LY2157299 in Fischer 344 rats and beagle dogs for up to six months of daily oral dosing. LY2157299 is well tolerated in the rat and dog for up to one month of daily dosing at doses of 150 and 20 mg/kg, respectively.
Results: In the rat, LY2157299 is well tolerated after three months of 2 weeks on/2 weeks off intermittent dosing schedule at 50 mg/kg. C.. View More»
DOI:
10.4172/2161-0495.196