生物活性

NecroX-7 is a potent free radical scavenger and a HMGB1 (high-mobility group box 1) inhibitor. NecroX-7 can be used as an antidote to acetaminophen toxicity. NecroX-7 exerts a protective effect by preventing the release of HMGB1 in ischemia/reperfusion injury. NecroX-7 inhibits the HMGB1-induced release of TNF and IL-6, as well as the expression of TLR-4 and receptor for advanced glycation end products. NecroX-7 can be used graft-versus-host disease (GVHD) research[1].

体外研究

NecroX-7 (0-40 μM, 3-4 d) inhibits activated or proliferating T cells without causing apoptosis [1]. NecroX-7 (0-40 μM) significantly lowers HMGB1 levels in a dose-dependent manner [1]. NecroX-7 inhibits formation of mitochondria-specific ROS/reactive nitrogen species in H9C2 cells and hepatocytes after induction by tert-butyl hydroperoxide or doxorubicin [1]. NecroX-7 increased regulatory T cell numbers, which may be associated with regulation of differentiation signals independent of HMGB1 [1]. Cell Proliferation Assay [1] Cell Line: CD4 T cells Concentration: 0, 0.625, 1.25, 2.5, 5, 10, 20, and 40 μM Incubation Time: 3-4 d Result: Showed a marked reduction in splenocyte proliferation, in a dose-dependent manner. Modulated alloreactive T cell responses.

体内研究

NecroX-7 (0-0.3 mg/kg, IV, once injection at 2-d intervals, for 2 weeks) markedly reduces GVHD-related mortality and inhibits severe tissue damage [1]. NecroX-7 protects mice against lethal GVHD by reciprocal regulation of regulatory T/Th1 cells, attenuating systemic HMGB1 accumulation and inhibiting HMGB1-mediated inflammatory response [1]. Animal Model: Female BALB/c and C57BL/6 mice (Eight-week-old, with GVHD) [1] Dosage: 0.03, 0.1, and 0.3 mg/kg Administration: IV, once injection at 2-d intervals, for 2 weeks Result: Observed statistically significant prolonged survival at doses ≥0.1 mg/kg: 30–60% of mice in these treatment groups survived for >50 d. Significantly improved clinical signs and prolonged survival, and the mice showed a reduction in clinical manifestations of acute GVHD, including weight loss, hunched posture, diarrhea, and ruffled fur.

激酶实验

细胞实验

动物实验

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1]. Im KI, et al. The Free Radical Scavenger NecroX-7 Attenuates Acute Graft-versus-Host Disease via Reciprocal Regulation of Th1/Regulatory T Cells and Inhibition of HMGB1 Release. J Immunol. 2015 Jun 1;194(11):5223-32.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

相关化合物库

使用AMQUAR产品发表文献后请联系我们