LY2157299 is a novel selective small molecule transforming growth factor beta receptor (TGF-¦ÂR) kinase inhibitor with IC50 of 86 nM and 2 nM for T¦ÂR1 and 2 nM, respectively. LY2157299 was well tolerated at both doses of 40 and 80 mg and no drug-related CTCAE Grade 3 or 4 toxicities were observed. Absorption of LY2157299 was rapid as determined by plasma concentrations at the first sampling time (0.5 hours). Daily oral administration of LY2157299 was safe and well tolerated at the two dose levels and the pharmacokinetic profile was consistent with the prediction derived from preclinical PK/PD model. As would be predicted for an inhibitor of TGF-¦Â signaling, LY2157299 blocked the phsophorylation of Smad2 but had no effect on fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF) signaling. However, another study reported that LY2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor- induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin -neutralizing antibody to the Matrigel selectively inhibited this enhanced response.

June 21, 2017

prudect name : LY2157299 is a novel selective small molecule transforming growth factor beta receptor (TGF-¦ÂR) kinase inhibitor with IC50 of 86 nM and 2 nM for T¦ÂR1 and 2 nM, respectively. LY2157299 was well tolerated at both doses of 40 and 80 mg and no drug-related CTCAE Grade 3 or 4 toxicities were observed. Absorption of LY2157299 was rapid as determined by plasma concentrations at the first sampling time (0.5 hours). Daily oral administration of LY2157299 was safe and well tolerated at the two dose levels and the pharmacokinetic profile was consistent with the prediction derived from preclinical PK/PD model. As would be predicted for an inhibitor of TGF-¦Â signaling, LY2157299 blocked the phsophorylation of Smad2 but had no effect on fibroblast growth factor (FGF) or platelet-derived growth factor (PDGF) signaling. However, another study reported that LY2157299 induced angiogenesis and enhanced VEGF- and basic-fibroblast-growth-factor- induced angiogenesis in a Matrigel-plug assay, whereas adding an alpha5-integrin -neutralizing antibody to the Matrigel selectively inhibited this enhanced response.
LY2157299

Synonyms: LY2157299CAS NO: 700874-72-2Molecular Formula: C22H19N5OMolecular Weight: 369.42Purity: 98% minSolubility: In DMSOStorage: −20°C


GDC 0032 References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18523147