DDO-7263, a 1,2,4-Oxadiazole derivative, is a potent Nrf2-ARE activator. DDO-7263 upregulates Nrf2 through binding to Rpn6 to block the assembly of 26S proteasome and the subsequent degradation of ubiquitinated Nrf2. DDO-7263 induces Nrf2 translocation in
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Product Description
DDO-7263, a 1,2,4-Oxadiazole derivative, is a potent Nrf2-ARE activator. DDO-7263 upregulates Nrf2 through binding to Rpn6 to block the assembly of 26S proteasome and the subsequent degradation of ubiquitinated Nrf2. DDO-7263 induces Nrf2 translocation into the nucleus. DDO-7263 inhibits of NLRP3 inflammasome activation. DDO-7263 exerts anti-inflammatory activity and has the potential for neurodegenerative diseases research, such as Parkinson's disease (PD).
In Vitro
DDO-7263 (20 μM; 2-24 h) can upregulate the protein levels of HO-1 and NQO1 in concentration-dependent manners. DDO-7263 (2.5, 5, 10, 20, 40, 80 μM; 24 h) can upregulate the survival rate of PC12 and THP-Ms cell after 400 μM H 2 O 2 in a concentration-dependent manner. DDO-7263 alone has no significant decrease on cell survival rate. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: PC12 cells Concentration: 20 μM Incubation Time: 2, 4, 8, 12, 24 hours Result: Upregulated the protein levels of HO-1 and NQO1 in concentration-dependent manners.
In Vivo
DDO-7263 (10-100 mg/kg/day; IP; for 10 days) improves the behavioral abnormalities induced by MPTP in mice, significantly attenuates chemically induced dopaminergic neuron loss of tyrosine hydroxylase (TH) in the substantia nigra (SN) and striatum of the mouse brain and inhibits the secretion of inflammatory factors . DDO-7263 (7, 35, 70 mg/kg; IP) has a T 1/2 of 3.32 hours and a C max of 1.38 mg/mL for rats . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male C57BL/6 mice at 10 weeks of age and body weights of 22-26 g Dosage: 10, 50, 100 mg/kg Administration: IP; daily for 10 days Result: Improved the reduction of vertical spontaneous activity and mitigated the loss of balance coordination caused by MPTP (20 mg/kg/day; 7 days). Protected dopaminergic neurons from MPTP. Significantly downregulated the levels of pro-inflammatory factors, including IL-1β and TNF-α, in mouse plasma. Animal Model: SD rats Dosage: 7, 35, 70 mg/kg (Pharmacokinetic Analysis) Administration: IP Result: Had a T 1/2 of 3.32 hours and a C max of 1.38 mg/mL.
Names and Identifiers
Smiles
CC1=NC=C(C2=NOC(C3=CC(F)=C(C=C3)F)=N2)C=C1
Molecular Weight
273.24
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