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Faculty, Staff and Student Publications Publication Date 10-18-2024 Journal Journal of Pharmacology and Experimental Therapeutics DOI 10.1124/jpet.124.002193 Abstract The development of transforming growth factor βreceptor inhibitors (TGFβRi) as new medicines has been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies.
Abstract The development of TGFβR inhibitors (TGFβRi) as new medicines have been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFβRI inhibitor (TGFβRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species.
Introduction The cytokine transforming growth factor (TGF)β suppresses early stages of carcinogenesis through tumor cell stasis and apoptosis (de Gouville and Huet, 2006; Prud'homme, 2007; Anderton et al., 2011; Colak and Ten Dijke, 2017). In later stages, TGFβ promotes tumor growth through evasion of tumor cell immune surveillance facilitating cancer cell dissemination and metastasis (Bierie and Moses, 2006; Massagué, 2008).
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