| Bioactivity | BAY-826 is a selective and potent TIE-2 inhibitor with a Kd of 1.6 nM, respectively. | ||||||||||||
| Invitro | 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. | ||||||||||||
| In Vivo | 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]. | ||||||||||||
| Name | BAY-826 | ||||||||||||
| CAS | 1448316-08-2 | ||||||||||||
| Formula | C26H19F5N6OS | ||||||||||||
| Molar Mass | 558.53 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
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| 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. |