SU5416 (Synonyms: NSC 696819, Semaxinib, Sugen 5416, VEGFR 2 Kinase Inhibitor)

Cell lines

Human microvascular endothelial cells of the lung-blood (HMVEC-LBl)

Preparation Method

Cells were plated into 24-well plates and grown to confluence in EGM-2MV medium containing 2.5% FBS plus supplements. Only cells in passage 5 were used, with n = 12 wells per experimental condition.

Reaction Conditions

HMVEC-LBl was exposed to human VEGF-121 (40 ng/mL) in-vitro in serum-free medium for 7 h, in the absence or presence of the VEGF receptor antagonist, SU5416 (3 and 10 μM).

Applications

SU5416 can block the effects of VEGF and completely prevent VEGFR2 phosphorylation as well. There was no evidence of background VEGFR2 phosphorylation in the HMVEC-LBl and in serum-free medium. Adding SU5416 did not affect the background phosphorylation. In the absence of VEGF, SU5416 increased ET-1 production, by 16% at 10 μM, and SU5416 can completely abolish the VEGF effect on ET-1 production.

Animal models

Wild-type C57BL/6 mice (male, 8–10 weeks, 20–24 g) and genetically engineered TLR4-deficient mice (male, 8–10 weeks, 20–22 g)

Preparation Method

Mice were stimulated by intratracheal administration of LPS after anesthetization with an intraperitoneal (i.p.) injection of tribromoethanol. Isopyknic saline-treated mice served as blank control group. After LPS stimulation, the experimental mice were treated with SU5416, DXM or DXM + SU5416 by oral administration for 12 hours. DXM-treated mice were served as positive control group.

Dosage form

20 mg/kg, BW solution in DMSO

Applications

SU5416 could be implemented to suppress immune response in mice with ALI. Normally, excessive activation and penetration of neutrophils is the common pathological process in LPS-induced ALI. Which subsequently enhanced the release of proinflammatory cytokines, which can further aggravate lung injury. SU5416 exhibited inhibitory effect on the population of neutrophil cell (P

References:

[1]. Star GP, et al. Effects of vascular endothelial growth factor on endothelin-1 production by human lung microvascular endothelial cells in vitro. Life Sci. 2014 Nov 24;118(2):191-4.

[2]. Huang X, et al. SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells. Drug Des Devel Ther. 2019 May 23;13:1763-1772.