Uses
NADPH oxidase-IN-1 is an orally active NADPH oxidase (Nox) inhibitor, related with neuronal inflammation. NADPH oxidase-IN-1 can cross the blood-brain barrier (BBB), inhibits Nox2 and Nox4 with IC50s of 1.9 μM and 2.47 μM, respectively. NADPH oxidase-IN-1 suppresses pro-inflammatory cytokines production and LPS-mediated microglial migration, also has in vivo efficacy[1].
in vivo
NADPH oxidase-IN-1 (compound 11) (30 mg/kg; p.o.; daily for 4 wk) attenuates MPTP induced microglia activation and diminishes dopaminergic neuronal damage in Parkinson's disease (PD) mice model[1].
NADPH oxidase-IN-1 is safe in both male and female mice following IV injection (10-300 mg/kg; single dose) and oral gavage (10-1000 mg/kg; single dose), respectively[1].
Pharmacokinetic profile in rats
| Parameters | C0 (μg/mL) | Cmax (μg/mL) | t1/2 (h) | Tmax (h) | AUClast (μg/h/mL) | ke (1/h) | Vd (L) | Vd/F (L) | Cl (L/h) | Cl/F (L/h) | F (%) |
| IV (2 mg/kg) | 1.70 | | 0.79 | | 0.468 | 1.32 | 0.211 | | 0.217 | | |
| PO (10 mg/kg) | | 0.609 | 5.01 | [0.083-2] | 1.31 | 0.170 | | 1.99 | | 0.341 | 56.0 |
| PO (20 mg/kg) | | 0.783 | 6.13 | [0.67-2] | 4.16 | 0.159 | | 1.82 | | 0.217 | 88.9 |
IC 50
NOX2: 1.9 μM (IC50); NOX4: 2.47 μM (IC50)
References
[1] Shim S, et al. Discovery of a NADPH oxidase inhibitor,(E)-3-cyclohexyl-5-(4-((2-hydroxyethyl)(methyl) amino) benzylidene)-1-methyl-2-thioxoimidazolidin-4-oneone, as a novel therapeutic for Parkinson's disease[J]. European Journal of Medicinal Chemistry, 2022, 244: 114854.
