Orantinib

Orantinib is an orally bioavailable receptor tyrosine kinase inhibitor. Orantinib binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. It is a potent ATP-competitive inhibitor of PDGFRbeta, VEGFR2, and FGFR1 (IC50 = 0.06, 2.4, and 3.0 µM, respectively) but not EGFR (IC50 >100 µM). Orantinib suppresses tumor growth, blocks angiogenesis in tumors and induces apoptosis of tumor vasculature and regression of established tumors. Orantinib inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells, inhibits Aurora kinases B and C (IC50=35 and 210nM, respectively), and inhibits Unc-51-like serine/threonine kinase Ulk3, involved in hedgehog signaling. All together ornatinib exhibits antiangiogenic, anti-inflammatory, antimetastatic and proapoptotic activity. Product References: (1) L. Sun, et al., J. Med. Chem. 42, 5120 (1999) , (2) A.D. Laird, et al., Cancer Res. 60, 4152 (2000) , (3) B.D. Smolich, et al., Blood 97, 1413 (2001) , (4) A.D. Laird, et al., FASEB J. 16, 681 (2002) , (5) K. Godl, et al., Cancer Res. 65, 6919 (2005) , (6) D.W. Kim, et al., J. Clin. Endocrinol. Metab. 91, 4070 (2006) , (7) J. Bain, et al., Biochem. J. 408, 297 (2007) , (8) M. Yamamoto, et al., Cancer Res. 68, 9754 (2008) , (9) N. Kammasud, et al., Bioorg. Med. Chem. Lett. 19, 745 (2009) , (10) A. Piirsoo, et al., Biochim. Biophys. Acta 1843, 703 (2014) , (11) L. Kasak, et al., Biochem. 57, 5456 (2018) Appearance: Orange to red solid. Solubility: Soluble in DMSO (10mg/ml) or DMF (5mg/ml). Identity: Determined by 1H-NMR. InChi Key: NHFDRBXTEDBWCZ-ZROIWOOFSA-N Smiles: O=C1NC2=CC=CC=C2/C1=C/C3=C(C)C(CCC(O)=O)=C(C)N3