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Updated: Aug 17, 2025
Author Spotlight: Overcoming Anti-VEGF Resistance Through Advanced Vascular Morphology Assessment in Choroidal Neovascularization
Published on: August 11, 2023
DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization
Huiying Zhang1, Bo Li2,3, Jingjuan Ding1
1The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
Abstract:
Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.
Insights
A novel drug, DCZ19931, effectively inhibits ocular neovascularization by targeting multiple pathways. This small molecule inhibitor shows promise for treating blinding eye diseases, offering an alternative to current anti-VEGF therapies.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Pathological neovascularization causes irreversible blindness in various eye diseases.
- Current anti-vascular endothelial growth factor (VEGF) therapies face challenges like ocular complications and drug resistance.
- Novel anti-angiogenic treatments are needed for ocular neovascularization.
Purpose of the Study:
- To investigate the anti-angiogenic effects of DCZ19931, a multi-target tyrosine kinase inhibitor, on ocular neovascularization.
- To evaluate the efficacy and safety of DCZ19931 in preclinical models of eye diseases.
Main Methods:
- Tested DCZ19931 in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) models.
- Assessed DCZ19931's effects on endothelial cell proliferation, migration, and tube formation in vitro.
- Investigated DCZ19931's impact on intercellular cell adhesion molecule-1 (ICAM-1) expression and MAPK signaling pathways (ERK1/2 and p38).
Main Results:
- DCZ19931 demonstrated no significant cytotoxicity or tissue toxicity.
- Reduced CNV lesion size and suppressed ocular neovascularization in OIR models.
- Inhibited VEGF-induced endothelial cell functions and reduced ICAM-1 levels, comparable to Ranibizumab.
- Inactivated ERK1/2-MAPK and p38-MAPK signaling pathways.
Conclusions:
- DCZ19931 exhibits potent anti-angiogenic effects in ocular disease models.
- The drug functions by inhibiting key signaling pathways involved in neovascularization.
- DCZ19931 represents a promising therapeutic candidate for anti-angiogenic therapy in ocular diseases.
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