BAY-826

• CAT Number: I020054
• CAS Number: 1448316-08-2
• Molecular Formula: C26H19F5N6OS
• Molecular Weight: 558.53
• Purity: ≥95%
• Synonyms: 3-cyano-N-[2,4-dimethyl-5-(6-pyridin-3-ylimidazo[1,2-b]pyrazol-1-yl)phenyl]-5-(pentafluoro-λ6-sulfanyl)benzamide
• InChI: InChI=1S/C26H19F5N6OS/c1-16-8-17(2)24(36-6-7-37-25(36)13-23(35-37)19-4-3-5-33-15-19)12-22(16)34-26(38)20-9-18(14-32)10-21(11-20)39(27,28,29,30)31/h3-13,15H,1-2H3,(H,34,38)
• InChIKey: MPASHPJAIUOWCK-UHFFFAOYSA-N
• SMILES: CC1=CC(=C(C=C1NC(=O)C2=CC(=CC(=C2)C#N)S(F)(F)(F)(F)F)N3C=CN4C3=CC(=N4)C5=CN=CC=C5)C

BAY-826 is a selective and potent TIE-2 inhibitor with a Kd of 1.6 nM, respectively.
BAY-826 is a selective and potent inhibitor of TIE-2 (dissociation constant = 1.6 nM) and binds with similar high affinity to only 4 of 456 tested kinases, namely, TIE-1, DDR1, DDR2, and Serine/threonine-protein kinase 10 (LOK) (dissociation constant = 0.9, 0.4,1.3, and 5.9 nM).The high biochemical affinity for TIE-2 translates into very potent cellular mechanistic activity with an EC50 of about 1.3 nM for inhibition of TIE-2 autophosphorylation in human umbilical vein endothelial cells. The TIE-2 inhibitor BAY-826 is tested for its acute growth inhibitory as well as anti-clonogenic properties in all four mouse glioma cell lines. BAY-826 is highly selective against other angiogenic kinases, such as VEGFR, fibroblast growth factorreceptor (FGFR), or Platelet-derived growth factor receptor (PDGFR), and affects VEGF-stimulated proliferation of HUVEC only atμM concentrations, respectively.
BAY-826 (oral gavage; 25 mg/kg,50 mg/kg,100 mg/k) potently inhibits ANG-1-stimulated TIE-2 autophosphorylation in murine lungs in female CB17/scid mice[1].
BAY-826 improves tumor control in syngeneic mouse glioma models. Co-treatment with BAY-826 and irradiation is ineffective in one model (SMA-497), but provided synergistic prolongation of survival in another (SMA-560) cell. TIE- 2 inhibition may improve tumor response to treatment in highly vascularized tumors such as glioblastoma[1].

Reference

[1]. Schneider H, et al. J Neurochem. 2017 Jan; 140(1):170-182. doi: 10.1111/jnc.13877. Epub 2016 Dec 12.Novel TIE-2 inhibitor BAY-826 displays in vivo efficacy in experimental syngeneic murine glioma models.
 [Content Brief]