NXPZ-2

• CAT Number: I043494
• CAS Number: 2254492-08-3
• Molecular Formula: C27H27N5O7S2
• Molecular Weight: 597.66
• Purity: ≥95%
• Synonyms: 2-[[4-[(2-amino-2-oxoethyl)-(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]-(4-aminophenyl)sulfonylamino]acetamide
• InChI: InChI=1S/C27H27N5O7S2/c1-39-19-8-12-21(13-9-19)41(37,38)32(17-27(30)34)25-15-14-24(22-4-2-3-5-23(22)25)31(16-26(29)33)40(35,36)20-10-6-18(28)7-11-20/h2-15H,16-17,28H2,1H3,(H2,29,33)(H2,30,34)
• InChIKey: DFIZGWXPFCOCFG-UHFFFAOYSA-N
• SMILES: COC1=CC=C(C=C1)S(=O)(=O)N(CC(=O)N)C2=CC=C(C3=CC=CC=C32)N(CC(=O)N)S(=O)(=O)C4=CC=C(C=C4)N

NXPZ-2 is an orally active Keap1-Nrf2 protein–protein interaction (PPI) inhibitor with a Ki value of 95 nM, EC50 value of 120 and 170 nM. NXPZ-2 can dose-dependently ameliorate Aβ[1-42]-Induced cognitive dysfunction, improve brain tissue pathological changes in Alzheimer’s disease (AD) mouse by increasing neuron quantity and function. NXPZ-2 can inhibit oxidative stress by increasing Nrf2 expression levels and promoting its cytoplasm to nuclear translocation, which is helpful for Keap1-Nrf2 PPI inhibitors and AD associated disease research[1].
NXPZ-2 (0-200 μM, 7 days) has no obvious toxicity on primary cortical neuron[1].
NXPZ-2 (Male ICR mice, 52.5/105/210 mg/kg, p.o., once daily for 7 days) improves AD mice learning and memorizing function including increased spontaneous alternation, increases number of active avoidance times, shortened escape latency, increased the time spent in the target quadrant and number of platform crossing[1].
NXPZ-2 (Male ICR mice, 52.5/105/210 mg/kg, p.o., once daily for 7 days) rescues the brain structure damage and lowers dead neuron numbers of AD mice with no obvious toxicity on mouse organs[1].
NXPZ-2 (Male ICR mice, 52.5/105/210 mg/kg, p.o., once daily for 7 days) alleviates oxidative stress by increasing Nrf2 expression levels, and promotes Nrf2’s cytoplasm to nuclear translocation, and improves cognitive dysfunction by elevating Nrf2 in both the central nervous system and peripheral blood[1].

Reference

[1]. Yi Sun, et al. Direct inhibition of Keap1-Nrf2 Protein-Protein interaction as a potential therapeutic strategy for Alzheimer’s disease. Bioorg Chem. 2020 Oct;103:104172.
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