NADPH oxidase-IN-1

• CAT Number: I042454
• CAS Number: 2762405-17-2
• Molecular Formula: C20H27N3O2S
• Molecular Weight: 373.51
• Purity: ≥95%
• Synonyms: (5E)-3-cyclohexyl-5-[[4-[2-hydroxyethyl(methyl)amino]phenyl]methylidene]-1-methyl-2-sulfanylideneimidazolidin-4-one
• InChI: InChI=1S/C20H27N3O2S/c1-21(12-13-24)16-10-8-15(9-11-16)14-18-19(25)23(20(26)22(18)2)17-6-4-3-5-7-17/h8-11,14,17,24H,3-7,12-13H2,1-2H3/b18-14+
• InChIKey: ZRIXYNJXSCQFPE-NBVRZTHBSA-N
• SMILES: CN1C(=CC2=CC=C(C=C2)N(C)CCO)C(=O)N(C1=S)C3CCCCC3

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].
NADPH oxidase-IN-1 (compound 11) can cross cross the blood-brain barrier (BBB) with Pe value of 13.6 (10-6 cm/s), determined by parallel artificial membrane permeability assay (PAMPA assay)[1].
NADPH oxidase-IN-1 (1 nM-10 mM; 30 min) LPS-induced ROS generation in BV2 microglial cells in a dose-dependent manner[1].
NADPH oxidase-IN-1 (10 μM; 24 h) inhibits the mRNA expression of pro-inflammatory cytokines in BV2 cells[1].
NADPH oxidase-IN-1 (1 nM-10 mM; 24 h) also inhibits activation and migration of BV2 cells[1].
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

Reference

[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.