BAY-826

Research use only, not for human use.

BAY-826 (BAY826) is a novel selective, highly potent, orally available TIE-2 inhibitor.

BAY-826 (BAY826) is a novel selective, highly potent, orally available TIE-2 inhibitor (dissociation constant=1.6 nM); binds with similar high affinity to only 4 of 456 kinases, namely, TIE-1,DDR1, DDR2, and LOK (dissociation constant=0.9, 0.4, 1.3, and 5.9 nM), BAY-826 is highly selective against other angiogenic kinases, such as VEGFR, FGFR, or PDGFR, and affects VEGF-stimulated proliferation of HUVEC only at lM concentrations; inhibits TIE-2 phosphorylation in vitro and in vivo as demonstrated by suppression of Angiopoietin-1- or Na3 VO4 -induced TIE-2 phosphorylation in glioma cells or extracts of lungs from BAY-826-treated mice; improves tumor control in syngeneic mouse glioma models.

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. 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.

BAY826

Tyrosine Kinase

Angiopoietin Receptor

Angiopoietin Receptor

Cancer

——

1448316-08-2

558.531

C26H19F5N6OS

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (179.04 mM)

O=C(NC1=CC(N2C=CN3N=C(C4=CC=CN=C4)C=C32)=C(C)C=C1C)C5=CC(S(F)(F)(F)(F)F)=CC(C#N)=C5

3-cyano-N-(2,4-dimethyl-5-(6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl)phenyl)-5-(pentafluoro-l6-sulfanyl)benzamide

(-20℃)

With Ice Pack

≥ 2 years