Ocuphire Pharma Results
In Vitro Validation of APX3330 Mechanism of Action
APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection
APX3330 reduces VEGF protein
expression in preclinical stroke model
VEGF
Control
VEGF
% Positive area (+SE)
2.6
1.3
0.0
Ocuphire
PHARMA
0.1mm
VEGF
APX3330
* p<0.05
n=7/group
T1DM-MCAO +APX3330
APX3330 reduces pro-inflammatory
cytokines in LPS stimulated macrophages
TNF-α
µg/mL
14000
12000
10000
8000
6000
4000
2000
0
APX3330
LPS (1 µg/mL)
14000
12000
10000
8000
5000
4000
2000
0
Hg/mL
0 ug/mL
APX3330
0 ug/mL
LPS (1 µg/mL)
0 ug/mL
+
25 ug/mL
+
Increasing APX3330 dose
6.3 ug/mL 12.5 ug/mL 25 ug/mL
+
+
+
IL-6
0 ug/mL
+
6.3 ug/mL 12.5 ug/mL
+
APX3330 increases DNA oxidative
repair and neuronal protection
Percentage increase in APE1
repair activity
120
115
110
105
100
95
90
N = 4
...
12.5
25
APX3330 (μM)
0
50
APX3330 enhances Ref-1 endonuclease
activity in dorsal root ganglion neurons
Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018
Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315
Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function
of APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017).
33View entire presentation