Dihydrochloride inhibits pathological retinal neovascularization
Animal study · C57BL/6J mice with oxygen-induced ischemic retinopathy; P12–P17 treatment [1]
At 25 mg/kg twice daily, retinal sections lacked surface neovascularization and deep capillary beds. Lower doses gave graded effects; the lowest dose did not significantly reduce endothelial staining in the reported t-test. Normal vascular development was also affected.
| Endpoint | Reported result | Reference |
|---|---|---|
| Endothelial cells above the internal limiting membrane | Histological presence/absence None identifiable at 25 mg/kg twice daily; deep capillary beds also absent | [1] |
| Area of retinal endothelial-cell staining | Dose response Significantly reduced at 2.5 and 25 mg/kg twice daily; lowest dose not significant by the stated paired t-test; dose-dependent trend P < 0.001 by ANOVA | [1] |
Conditions shared by the study groups
- Route
- Oral gavage
- Vehicle
- Shared method specifies aqueous buffer or DMSO depending on solubility, diluted with water (maximum 1% DMSO); exact PTK787 formulation is not assigned.
| Group / dose | Comparator | Observed result | Reference |
|---|---|---|---|
| PTK787 dose range 0.25, 2.5 or 25 mg/kg per dose | Vehicle-treated mice with ischemic retinopathy; nonischemic mice as reference | Dose-dependent inhibition; complete absence of surface neovascularization at 25 mg/kg twice daily. Lowest dose did not meet the stated t-test significance threshold. | [1] |
| Separate CGP 57148 and CGP 53716 comparator groups 120 μmoles/kg/day, as reported | Vehicle-treated ischemic mice | Neither comparator showed an apparent decrease in neovascularization; CGP 57148 was also quantified. This observation alone does not validate target selectivity. | [1] |
- PTK787 dose range
- Frequency: Twice daily
- Treatment course: 5 days, P12–P17
- Separate CGP 57148 and CGP 53716 comparator groups
- Frequency: Twice daily, per shared treatment method
- Treatment course: 5 days
- Reported limits: Comparator target-selectivity values are not adopted; one cited historical source is retracted.
Methods and source locations
Compound reported in the paper: Vatalanib (PTK787/ZK222584); Compound label in the paper: PTK787 dihydrochloride
Supports this salt in a mouse retinal model; no general efficacy or safety claim.
Materials and Methods: Drug Treatment of Mice with Ischemic Retinopathy; Quantitation of Retinal Neovascularization; Results: PTK787 Inhibits Retinal Neovascularization in Mice with Ischemic Retinopathy; Figures 1–2
Endothelial cells above the internal limiting membrane: Lectin-stained retinal sections; vehicle-treated ischemic and nonischemic controls. — Figure 1E–F and associated Results
Area of retinal endothelial-cell staining: Thirteen sections per eye averaged as one experimental value. Figure 2E labels N=8 for each PTK787 group and each control. Exact bar heights not transcribed. — Figure 2E; Results paragraphs on 2.5 and 0.25 mg/kg twice daily
PTK787 dose range · Figures 1–2; associated Results
Separate CGP 57148 and CGP 53716 comparator groups · Figure 2A–E and associated Results