APX-115 free base
(Synonyms: Ewha-18278 free base) 目录号 : GC38115Isuzinaxib (APX-115 free base, Ewha-18278 free base) is a potent, orally active inhibitor of pan NADPH oxidase (pan-Nox) with Ki of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 free base (Ewha-18278 free base) significantly suppresses the expression of inflammatory molecules including MCP-1/CCL2, IL-6, and TNFα in the diabetic kidney.
Cas No.:1270084-92-8
Sample solution is provided at 25 µL, 10mM.
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Isuzinaxib (APX-115 free base, Ewha-18278 free base) is a potent, orally active inhibitor of pan NADPH oxidase (pan-Nox) with Ki of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 free base (Ewha-18278 free base) significantly suppresses the expression of inflammatory molecules including MCP-1/CCL2, IL-6, and TNFα in the diabetic kidney.
[1] Jung Hee Joo, et al. Sci Rep. 2016 Mar 15;6:22389. [2] Jin Joo Cha, et al. Lab Invest. 2017 Apr;97(4):419-431.
Cas No. | 1270084-92-8 | SDF | |
别名 | Ewha-18278 free base | ||
Canonical SMILES | OC1=C(CCC)C(C2=CC=CC=C2)=NN1C3=NC=CC=C3 | ||
分子式 | C17H17N3O | 分子量 | 279.34 |
溶解度 | DMSO: 250 mg/mL (894.97 mM) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg | |
1 mM | 3.5799 mL | 17.8993 mL | 35.7987 mL |
5 mM | 0.716 mL | 3.5799 mL | 7.1597 mL |
10 mM | 0.358 mL | 1.7899 mL | 3.5799 mL |
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APX-115, a first-in-class pan-NADPH oxidase (Nox) inhibitor, protects db/db mice from renal injury
Lab Invest 2017 Apr;97(4):419-431.PMID:28165467DOI:10.1038/labinvest.2017.2.
Recent studies have suggested that renal Nox is important in the progression of diabetic nephropathy. Therefore, we investigated the effect of a novel pan-NOX-inhibitor, APX-115, on diabetic nephropathy in type 2 diabetic mice. Eight- week-old db/m and db/db mice were treated with APX-115 for 12 weeks. APX-115 was administered by oral gavage at a dose of 60 mg/kg per day. To compare the effects of APX-115 with a dual Nox1/Nox4 inhibitor, db/db mice were treated with GKT137831 according to the same protocol. APX-115 significantly improved insulin resistance in diabetic mice, similar to GKT137831. Oxidative stress as measured by plasma 8-isoprostane level was decreased in the APX-115 group compared with diabetic controls. All lipid profiles, both in plasma and tissues improved with Nox inhibition. APX-115 treatment decreased Nox1, Nox2, and Nox4 protein expression in the kidney. APX-115 decreased urinary albumin excretion and preserved creatinine level. In diabetic kidneys, APX-115 significantly improved mesangial expansion, but GKT137831 did not. In addition, F4/80 infiltration in the adipose tissue and kidney decreased with APX-115 treatment. We also found that TGF-β stimulated ROS generation in primary mouse mesangial cells (pMMCs) from wild-type, Nox1 KO, and Duox1 KO mice, but did not induce Nox activity in pMMCs from Nox2 knockout (KO), Nox4 KO, or Duox2 KO mice. These results indicate that activating Nox2, Nox4, or Duox2 in pMMCs is essential for TGF-β-mediated ROS generation. Our findings suggest that APX-115 may be as effective or may provide better protection than the dual Nox1/Nox4 inhibitor, and pan-Nox inhibition with APX-115 might be a promising therapy for diabetic nephropathy.