advertisement
Abstract #126938 Published in IGR 25-2
Identification of Nitric Oxide Donating Dasatinib Derivatives with Intraocular Pressure Lowering and Senolytic Activities
Pan Z; Zhang J; Zuo H; Li C; Song H; Yang H; Wu K; Zhao M; Zhang Z; Lai Y; Luo J; Wu J; Zhao L; Huang ZJournal of Medicinal Chemistry 2025; 68: 8600-8617
Based on two major risk factors of glaucoma, elevated intraocular pressure (IOP) and senescence, two new series of nitric oxide (NO) donating dasatinib derivatives-, - were designed, synthesized, and biologically evaluated. The results demonstrated that the most active compound effectively released NO and increased the concentration of 3',5'-cyclic guanosine monophosphate in human trabecular meshwork cells, as well as maintained senolytic activity. Topical administration of in chronic ocular hypertension (COHT) glaucoma mice not only significantly eliminated senescent cells in retina but also exhibited potent retinal ganglion cells (RGCs) surviving, IOP lowering, and visual function protection activities, which were superior to those of dasatinib. Compared with younger adult mice, aged COHT mice resulted in more severe RGCs loss, while demonstrated a greater capacity to improve RGCs survival. Our findings show that dual IOP lowering and senolytic functions could be a promising therapeutic strategy for glaucoma, particularly in older patients.
Full article
