LY 364947 is a diheteroaryl-substituted pyrazole compound used as a selective, ATP-competitive inhibitor of TGF-βRI (TGF-β Receptor I kinase). Studies of mouse fibroblasts show that LY 364947 inhibits cellular growth and transcription activation via TGF-β Receptor I kinase inhibition. In addition, TGF-β Receptor I kinase is responsible for fibroblast proliferation and the accumulation of astrocytes around the fibrotic scar when injury occurs to cells. In vitro studies report that in the presence of LY 364947 the amount of reactive astrocytes at the lesion site is also reduced. Furthermore, studies show that LY 364947 strongly effects intraplug vasculature by increasing the extravasation of Dextran (sc-218165). LY 364947 is an inhibitor of eIF2 alpha, MLTK, p38 alpha and TGF β RII.
1. Kano, M.R., et al. 2009. Cancer Sci. 100: 173-180. PMID: 19037999 2. Yoshioka, N., et al. 2010. J Neurosci Res. [Epub ahead of print]. PMID: 21181763 3. Kimura-Kuroda, J., et al. 2010. Mol. Cell. Neurosci. 43: 177-187. PMID: 19897043
Soluble in DMSO (100 mM), water (<1 mg/ml at 25° C), ethanol (<1 mg/ml at 25° C), DMF (~0.1 mg/ml), and 1:1 DMF:PBS (pH 7.2) (~0.5 mg/ml).
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NassarNassar, K. et al. (PubMed 24742493) evaluated the use of the TGF- receptor 1 inhibitor LY 364947 to prevent proliferative vitreoretinopathy (PVR). They found that LY 364947 reduces Human Tenon's Fibroblast proliferation and retinal pigment epithelial transdifferentiation in vitro and prevents proliferative vitreoretinopathy and subsequent tractional retinal detachment in vivo. -SCBT Publication Review
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