SKLB1002 is a potent inhibitor of VEGF receptor 2 signaling. SKLB1002 administration significantly reduced endothelial cell proliferation, migration and tube formation in vitro. Mechanistically, SKLB1002 inhibited endothelial angiogenic functions by blocking the phosphorylation of ERK1/2, JNK and p38[3]. Compared with the solvent control, administration of 100 mg/kg/d SKLB1002 reached more than 60% inhibition against human tumor xenografts in athymic mice[4]. Inhibition of VEGF signalling using SKLB1002 increased ROBO4 (Roundabout-4) expression and reduced neovascularisation indices. Furthermore, SKLB1002 significantly decreased ROBO4-β3 integrin interaction in diabetes[5].
SKLB1002 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human umbilical vein endothelial cells (HUVECs)
10 or 50 nM
24 hours
To assess the effect of SKLB1002 on VEGF-induced proliferation, migration, and tube formation in HUVECs, results showed significant inhibition of these functions
Mol Med Rep. 2020 Jun;21(6):2571-2579.
Human umbilical vein endothelial cells (HUVECs)
1 to 100 nM
48 hours
To evaluate the cytotoxicity of SKLB1002 on HUVECs, results showed no obvious cytotoxicity at concentrations ranging from 1 to 100 nM
Mol Med Rep. 2020 Jun;21(6):2571-2579.
HCT116 cells
10 ng/mL
24 hours
SKLB1002 inhibited the ability of HCT116 cells to form tube-like structures and reduced VE-cadherin expression.
BMC Cancer. 2017 Aug 30;17(1):593.
SKLB1002 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
ICR mice
Alkali-burn corneal model
Eyedrop
0.05 mg/ml
3 times per day for 7 days
To evaluate the inhibitory effect of SKLB1002 on corneal neovascularization, results showed significant reduction in the number and length of new blood vessels
Mol Med Rep. 2020 Jun;21(6):2571-2579.
Rats
Type 2 diabetic GK rat model
Intraperitoneal injection
10 mg/kg body weight
Once daily for 2 weeks
To inhibit VEGFR-2 activation, increase ROBO4 expression, and reduce cerebral neovascularisation
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