Uses
Emixustat is an orally active RPE65 inhibitor with an IC50 value of 4.4 nM. Emixustat is also a visual cycle modulator, capable of regulating visual cycle activity by inhibiting retinol isomerization, and holds potential for studying vision disorders such as age-related macular degeneration (AMD)[1][2][3][4].
in vivo
Emixustat (1-10 mg/kg, oral administration, single dose, or twice daily for 6 days; 1 mg/kg, i.p., measurement after 30-60 minutes) reduced cation influx and oxygen consumption in the retinas of brown Norway rats under dark adaptation conditions[3].
Emixustat (0.03-3.0 mg/kg, intravenous injection, once daily for 5 days) inhibits neovascularization and protects the retina in the oxygen-induced retinopathy mouse model[4].
| Animal Model: | Brown norway rats (200-300 g, 3 months old)[3] |
| Dosage: | 1, 5 or 10 mg/kg |
| Administration: | Oral gavage (p.o.), single dose (1, 10 mg/kg), 2 hours followed by 4 hours of dark adaptation, or twice a day for 6 days (5 mg/kg) |
| Result: | Reduced the conductance of the retinal cation channels after dark adaptation. |
| Animal Model: | Brown norway rats (200-300 g, 3 months old)[3] |
| Dosage: | 1 mg/kg |
| Administration: | Intravenous injection (i.v.), retinal PO2 was measured 30-60 min later |
| Result: | Reduced the oxygen consumption during dark adaptation. |
| Animal Model: | Oxygen-induced retinopathy (OIR) mice model (BALB/c and 129/Sv / C57BL/6 mixed background) |
| Dosage: | 0.03, 0.1, 0.3, 1.0, 3.0 mg/kg |
| Administration: | Intravenous injection (i.v.), once daily for 5 days |
| Result: | Dose-dependently reduced retinal neovascularization. |
References
[1] Bavik C, et al. Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. DOI:
10.1371/journal.pone.0124940[2] Kiser PD, et al. Catalytic mechanism of a retinoid isomerase essential for vertebrate vision. Nat Chem Biol. 2015 Jun;11(6):409-15. DOI:
10.1038/nchembio.1799[3] Kubota R, et al. Emixustat Reduces Metabolic Demand of Dark Activity in the Retina. Invest Ophthalmol Vis Sci. 2019 Nov 1;60(14):4924-4930. DOI:
10.1167/iovs.19-28194[4] Bavik C, et al. Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity. PLoS One. 2015 May 13;10(5):e0124940. DOI:
10.1371/journal.pone.0124940
